Plants having increased tolerance to herbicides

ABSTRACT

The present invention refers to a plant or plant part comprising a polynucleotide encoding a wildtype or mutated cellulose synthase (CESA) polypeptide, the expression of said polynucleotide confers to the plant or plant part tolerance to CESA-inhibiting herbicides, such as azines.

This application is a National Stage application of InternationalApplication No. PCT/EP2015/058633, filed Apr. 22, 2015, which claims thebenefit of U.S. Patent Application Nos. 61/982,893, 61/982,894,61/982,895, 61/982,896, 61/982,897, 61/982,898, 61/982,899, 61/982,900,61/982,901, 61/982,903, 61/982,904, which were all filed on Apr. 23,2014, and the contents of which are incorporated herein by reference intheir entirety.

INCORPORATION BE REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY

This application incorporates by reference in its entirety acomputer-readable nucleotide/amino acid sequence listing identified asone 635,311 byte ASCII (text) file named “76908_Seqlisting.txt,” createdOct. 12, 2016.

FIELD OF THE INVENTION

The present invention relates in general to methods for conferring onplants agricultural level tolerance to herbicides. Particularly, theinvention refers to plants having an increased tolerance to herbicides,more specifically to herbicides which inhibit the enzyme cellulosesynthase (CESA), also known cellulose biosynthesis inhibitors (CBI).More specifically, the present invention relates to methods and plantsobtained by mutagenesis and cross-breeding and transformation that havean increased tolerance to herbicides, particularly CESA-inhibitingherbicides.

BACKGROUND OF THE INVENTION

Plant cell walls are complex structures composed ofhigh-molecular-weight polysaccharides, proteins, and lignins. Among thewall polysaccharides, cellulose, a hydrogen-bonded β-1,4-linked glucanmicrofibril, is the main load-bearing wall component and a key precursorfor industrial applications. Cellulose is synthesized by largemultimeric cellulose synthase (CESA) complexes (E.C.2.4.1.12), trackingalong cortical microtubules at the plasma membrane. The only knowncomponents of these complexes are the cellulose synthase proteins.Recent studies have identified tentative interaction partners for theCESAs and shown that the migratory patterns of the CESA complexes dependon phosphorylation status (for review see Endler and Persson, MolecularPlant, 2011, Volume 4, Number 2, Pages 199-211, and references containedtherein). For example, cotton cellulose synthase genes, termed CESA1 andCESA2, were identified in a collection of expressed sequence tag (EST)sequences on the basis of weak sequence similarity to genes forcellulose synthase from bacteria (Richmond and Somerville. PlantPhysiology, 2000, Vol. 124, 495-498; and references contained therein)In addition, the genes were expressed at high levels in cotton fibers atthe onset of secondary wall synthesis and a purified fragment of one ofthe corresponding proteins as shown to bind UDP-Glc, the proposedsubstrate for cellulose biosynthesis. The conclusion that the cottonCESA genes are cellulose synthases is supported by results obtained withtwo cellulose-deficient Arabidopsis mutants, rsw1 and irx3 (Richmond andSomerville. Plant Physiology, Vol. 124, 2000, 495-498; and referencescontained therein). The genes corresponding to the RSW1 and IRX3 lociexhibit a high degree of sequence similarity to the cotton CESA genesand are considered orthologs. Ten full-length CESA genes have beensequenced from Arabidopsis, and there is a genome survey sequence thatmay indicate one additional family member. Reiterative database searchesusing the Arabidopsis Rsw1 (AtCESA1) and the cotton CESA polypeptidesequences as the initial query sequences revealed a large superfamily ofat least 41 CESA-like genes in Arabidopsis. Based on predicted proteinsequences, these genes were grouped into seven clearly distinguishablefamilies (Richmond and Somerville. Plant Physiology, Vol. 124, 2000,495-498; and references contained therein): the CESA family, whichincludes RSW1 and IRX3 (AtCESA7), and six families of structurallyrelated genes of unknown function designated as the “cellulosesynthase-like” genes (CsIA, CsIB, CsIC, CsID, CsIE, and CsIG).

WO 2013/142968 describes plant cellulose synthase (CESA) allelesidentified by mutagenizing plants and screening said plants with acellulose biosynthetic inhibitor (CBI). CBIs employed in WO 2013/142968include dichlobenil, chlorthiamid, isoxaben, flupoxam, and quinclorac,particularly isoxaben or flupoxam (named fpx1-1 to fxp1-3 [CESA3],fxp2-1 to fxp2-3 [CESA1] and ixr1-1 to ixr1-7 [CESA3], ixr2-1 to ixr2-2[CESA6] mutants of Arabidopsis CESA wildtype enzymes)

The inventors of the present invention have now surprisingly found thatover-expression of the mutant cellulose synthase forms disclosed in WO2013/142968 confers in plants tolerance/resistance to particular classesof CESA-inhibiting herbicides (cellulose biosynthesis inhibitors; CBIs)as compared to the non-transformed and/or non-mutagenized plants orplant cells, respectively. More specifically, the inventors of thepresent invention have found that CESA expression conferstolerance/resistance to azines. More specifically, the inventors of thepresent invention have found that modifications of the C-terminal partof CESA proteins confer tolerance/resistance to azines.

The problem of the present invention can be seen as to the provision ofnovel traits by identifying target polypeptides, the manipulation ofwhich makes plants tolerant to herbicides.

Three main strategies are available for making plants tolerant toherbicides, i.e. (1) detoxifying the herbicide with an enzyme whichtransforms the herbicide, or its active metabolite, into non-toxicproducts, such as, for example, the enzymes for tolerance to bromoxynilor to basta (EP242236, EP337899); (2) mutating the target enzyme into afunctional enzyme which is less sensitive to the herbicide, or to itsactive metabolite, such as, for example, the enzymes for tolerance toglyphosate (EP293356, Padgette S. R. et al., J. Biol. Chem., 266, 33,1991); or (3) overexpressing the sensitive enzyme so as to producequantities of the target enzyme in the plant which are sufficient inrelation to the herbicide, in view of the kinetic constants of thisenzyme, so as to have enough of the functional enzyme available despitethe presence of its inhibitor.

The problem is solved by the subject-matter of the present invention.

SUMMARY OF THE INVENTION

Accordingly, in one aspect, the present invention provides a plant orplant part comprising a polynucleotide encoding a wildtype or mutatedCESA polypeptide, the expression of said polynucleotide confers to theplant or plant part tolerance to CESA-inhibiting herbicides.

In some aspects, the present invention provides a seed capable ofgermination into a plant comprising in at least some of its cells apolynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto CESA-inhibiting herbicides.

In one aspect, the present invention provides a plant cell of or capableof regenerating a plant comprising in at least some of its cells apolynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto CESA-inhibiting herbicides, wherein the plant cell comprises thepolynucleotide operably linked to a promoter.

In another aspect, the present invention provides a plant cellcomprising a polynucleotide operably linked to a promoter operable in acell, the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto CESA-inhibiting herbicides.

In other aspects, the present invention provides a plant productprepared from a plant or plant part comprising in at least some of itscells a polynucleotide operably linked to a promoter operable in plantcells, the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto CESA-inhibiting herbicides.

In some aspects, the present invention provides a progeny or descendantplant derived from a plant comprising in at least some of its cells apolynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, wherein the progeny ordescendant plant comprises in at least some of its cells the recombinantpolynucleotide operably linked to the promoter, the expression of thewildtype or mutated CESA polypeptide conferring to the progeny ordescendant plant tolerance to the CESA-inhibiting herbicides.

In other aspects, the present invention provides a method forcontrolling weeds at a locus for growth of a plant, the methodcomprising: (a) applying an herbicide composition comprisingCESA-inhibiting herbicides to the locus; and (b) planting a seed at thelocus, wherein the seed is capable of producing a plant that comprisesin at least some of its cells a polynucleotide operably linked to apromoter operable in plant cells, the promoter capable of expressing awildtype or mutated CESA polypeptide encoded by the polynucleotide, theexpression of the wildtype or mutated CESA polypeptide conferring to theplant tolerance to CESA-inhibiting herbicides.

In some aspects, the present invention provides a method for controllingweeds at a locus for growth of a plant, the method comprising: applyingan herbicidal composition comprising CESA-inhibiting herbicides to thelocus; wherein said locus is: (a) a locus that contains: a plant or aseed capable of producing said plant; or (b) a locus that is to be aftersaid applying is made to contain the plant or the seed; wherein theplant or the seed comprises in at least some of its cells apolynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto CESA-inhibiting herbicides.

In one aspect, step (a) occurs before, after, or concurrently with step(b).

In other aspects, the present invention provides a method of producing aplant having tolerance to CESA-inhibiting herbicides, the methodcomprising regenerating a plant from a plant cell transformed with apolynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto CESA-inhibiting herbicides.

In one aspect, the present invention provides a method of producing aprogeny plant having tolerance to CESA-inhibiting herbicides, the methodcomprising: crossing a first CESA-inhibiting herbicides-tolerant plantwith a second plant to produce a CESA-inhibiting herbicides-tolerantprogeny plant, wherein the first plant and the progeny plant comprise inat least some of their cells a polynucleotide operably linked to apromoter operable in plant cells, the promoter capable of expressing awildtype or mutated CESA polypeptide encoded by the polynucleotide, theexpression of the wildtype or mutated CESA polypeptide conferring to theplant tolerance to CESA-inhibiting herbicides.

In addition, the present invention refers to a method for identifying aCESA-inhibiting herbicide by using a wildtype or mutated CESA of thepresent invention encoded by a nucleic acid which comprises thenucleotide sequence of SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72, 73,74, 75, 76, or 77, or a variant, homologue, paralogue or orthologuethereof.

Said method comprises the steps of:

-   a) generating a transgenic cell or plant comprising a nucleic acid    encoding a wildtype or mutated CESA of the present invention,    wherein the wildtype or mutated CESA of the present invention is    expressed;-   b) applying a CESA-inhibiting herbicide to the transgenic cell or    plant of a) and to a control cell or plant of the same variety;-   c) determining the growth or the viability of the transgenic cell or    plant and the control cell or plant after application of said test    compound, and-   d) selecting test compounds which confer reduced growth to the    control cell or plant as compared to the growth of the transgenic    cell or plant.

Another object refers to a method of identifying a nucleotide sequenceencoding a wildtype or mutated CESA which is resistant or tolerant to aCESA-inhibiting herbicide, the method comprising:

-   a) generating a library of wildtype or mutated CESA-encoding nucleic    acids,-   b) screening a population of the resulting wildtype or mutated    CESA-encoding nucleic acids by expressing each of said nucleic acids    in a cell or plant and treating said cell or plant with a    CESA-inhibiting herbicide,-   c) comparing the CESA-inhibiting herbicide-tolerance levels provided    by said population of wildtype or mutated CESA encoding nucleic    acids with the CESA-inhibiting herbicide-tolerance level provided by    a control CESA-encoding nucleic acid,-   d) selecting at least one wildtype or mutated CESA-encoding nucleic    acid that provides a significantly increased level of tolerance to a    CESA-inhibiting herbicide as compared to that provided by the    control CESA-encoding nucleic acid.

In a preferred embodiment, the wildtype or mutated CESA-encoding nucleicacid selected in step d) provides at least 2-fold as much tolerance to aCESA-inhibiting herbicide as compared to that provided by the controlCESA-encoding nucleic acid.

The resistance or tolerance can be determined by generating a transgenicplant comprising a nucleic acid sequence of the library of step a) andcomparing said transgenic plant with a control plant.

Another object refers to a method of identifying a plant or algaecontaining a nucleic acid encoding a wildtype or mutated CESA which isresistant or tolerant to a CESA-inhibiting herbicide, the methodcomprising:

-   a) identifying an effective amount of a CESA-inhibiting herbicide in    a culture of plant cells or green algae.-   b) treating said plant cells or green algae with a mutagenizing    agent,-   c) contacting said mutagenized cells population with an effective    amount of CESA-inhibiting herbicide, identified in a),-   d) selecting at least one cell surviving these test conditions,-   e) PCR-amplification and sequencing of CESA genes from cells    selected in d) and comparing such sequences to wild-type CESA gene    sequences, respectively.

In a preferred embodiment, the mutagenizing agent isethylmethanesulfonate.

Another object refers to an isolated recombinantly produced, and/orchemically synthesized nucleic acid encoding a wildtype or mutated CESA,the nucleic acid comprising the sequence of SEQ ID NO: 65, 66, 67, 68,69, 70, 71, 72, 73, 74, 75, 76, or 77, or a variant thereof, as definedhereinafter.

In a preferred embodiment, the nucleic acid being identifiable by amethod as defined above.

Another object refers to an isolated, recombinantly produced, and/orchemically synthesized wildtype or mutated CESA polypeptide, thepolypeptide comprising the sequence set forth in SEQ ID NO: 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, or 64, a variant, derivative, orthologue, paralogue orhomologue thereof, as defined hereinafter.

In still further aspects, the present invention provides a plant orplant part comprising in at least some of its cells a polynucleotideoperably linked to a promoter operable in plant cells, the promotercapable of expressing a wildtype or mutated CESA polypeptide encoded bythe polynucleotide, the expression of the wildtype or mutated CESApolypeptide conferring to the plant tolerance to CESA-inhibitingherbicides, wherein the plant or plant part further exhibits a second orthird herbicide-tolerant trait.

In another embodiment, the invention refers to a plant cell transformedby and expressing a a wildtype or mutated CESA nucleic acid according tothe present invention or a plant which has been mutated to obtain aplant expressing, preferably over-expressing a a wildtype or mutatedCESA nucleic acid according to the present invention, wherein expressionof said nucleic acid in the plant cell results in increased resistanceor tolerance to a CESA-inhibiting herbicide as compared to a wild typevariety of the plant cell

In another embodiment, the invention refers to a plant comprising aplant cell according to the present invention, wherein expression of thenucleic acid in the plant results in the plant's increased resistance toCESA-inhibiting herbicide as compared to a wild type variety of theplant.

The plants of the present invention can be transgenic or non-transgenic.

Preferably, the expression of the nucleic acid of the invention in theplant results in the plant's increased resistance to CESA-inhibitingherbicides as compared to a wild type variety of the plant. In anotherembodiment, the invention refers to a seed produced by a transgenicplant comprising a plant cell of the present invention, wherein the seedis true breeding for an increased resistance to a CESA-inhibitingherbicide as compared to a wild type variety of the seed.

In another embodiment, the invention refers to a method of producing atransgenic plant cell with an increased resistance to a CESA-inhibitingherbicide as compared to a wild type variety of the plant cellcomprising, transforming the plant cell with an expression cassettecomprising a a polynucleotide operably linked to a promoter operable inplant cells, the promoter capable of expressing a wildtype or mutatedCESA polypeptide encoded by the polynucleotide.

In another embodiment, the invention refers to a method of producing atransgenic plant comprising, (a) transforming a plant cell with anexpression cassette comprising a a polynucleotide operably linked to apromoter operable in plant cells, the promoter capable of expressing awildtype or mutated CESA polypeptide encoded by the polynucleotide, and(b) generating a plant with an increased resistance to CESA-inhibitingherbicide from the plant cell.

Preferably, the expression cassette further comprises a transcriptioninitiation regulatory region and a translation initiation regulatoryregion that are functional in the plant.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 A, B, C

FIG. 1 shows phylogenetic trees of cellulose synthase homologues in corn(A), soy (B) and rice (C).

FIG. 2 A, B, C

FIG. 2 shows alignment of all cellulose synthase homologues (A),arabidopsis CESA1, CESA3 and CESA 6 homologues (B) and Arabidopsis CESA1and CESA3 homologues (C).

KEY TO SEQUENCE LISTING

TABLE 1 SEQ ID NO Amino acid Sequence/Origin 1 At_CESA1 2 At_CESA2 3At_CESA3 4 At_CESA4 5 At_CESA5 6 At_CESA6 7 At_CESA7 8 At_CESA8 9At_CESA9 10 At_CESA10 11 GRMZM2G027723|GRMZM2G027723_T01 12GRMZM2G055795|GRMZM2G055795_T01 13 GRMZM2G039454|GRMZM2G039454_T01 14GRMZM2G025231|GRMZM2G025231_T02 15 GRMZM2G142898|GRMZM2G142898_T01 16GRMZM2G424832|GRMZM2G424832_T01 17 GRMZM2G177631|GRMZM2G177631_T01 18GRMZM2G150404|GRMZM2G150404_T01 19 GRMZM2G028353|GRMZM2G028353_T01 20GRMZM2G018241|GRMZM2G018241_T01 21 GRMZM2G037413|GRMZM2G037413_T01 22GRMZM2G082580|GRMZM2G082580_T01 23 GRMZM2G112336|GRMZM2G112336_T01 24GRMZM2G111642|GRMZM2G111642_T01 25 GRMZM2G113137|GRMZM2G113137_T01 26Glyma02g36720|Glyma02g36720.1 27 Glyma02g08920|Glyma02g08920.1 28Glyma12g36570|Glyma12g36570.1 29 Glyma12g17730|Glyma12g17730.1 30Glyma06g06870|Glyma06g06870.1 31 Glyma06g30860|Glyma06g30860.1 32Glyma06g47420|Glyma06g47420.1 33 Glyma06g30850|Glyma06g30850.1 34Glyma06g07320|Glyma06g07320.1 35 Glyma04g07220|Glyma04g07220.1 36Glyma04g06780|Glyma04g06780.1 37 Glyma04g23530|Glyma04g23530.2 38Glyma08g15380|Glyma08g15380.1 39 Glyma08g12400|Glyma08g12400.1 40Glyma17g08000|Glyma17g08000.1 41 Glyma13g27250|Glyma13g27250.3 42Glyma05g29240|Glyma05g29240.2 43 Glyma05g32100|Glyma05g32100.1 44Glyma15g43040|Glyma15g43040.1 45 Glyma09g15620|Glyma09g15620.2 46Glyma10g36790|Glyma10g36790.1 47 Glyma16g28080|Glyma16g28080.2 48Os01g54620.1 49 Os03g59340.1 50 Os03g62090.1 51 Os05g08370.1 52Os06g02180.1 53 Os06g22980.1 54 Os06g39970.1 55 Os07g10770.1 56Os07g14850.1 57 Os07g24190.1 58 Os07g24190.2 59 Os07g24190.3 60Os08g25710.1 61 Os09g25490.1 62 Os10g32980.1 63 Os10g42750.1 64Os12g36890.1

DETAILED DESCRIPTION

The articles “a” and “an” are used herein to refer to one or more thanone (i.e., to at least one) of the grammatical object of the article. Byway of example, “an element” means one or more elements.

As used herein, the word “comprising,” or variations such as “comprises”or “comprising,” will be understood to imply the inclusion of a statedelement, integer or step, or group of elements, integers or steps, butnot the exclusion of any other element, integer or step, or group ofelements, integers or steps.

The term “control of undesired vegetation or weeds” is to be understoodas meaning the killing of weeds and/or otherwise retarding or inhibitingthe normal growth of the weeds. Weeds, in the broadest sense, areunderstood as meaning all those plants which grow in locations wherethey are undesired. The weeds of the present invention include, forexample, dicotyledonous and monocotyledonous weeds. Dicotyledonous weedsinclude, but are not limited to, weeds of the genera: Sinapis, Lepidium,Galium, Stellaria, Matricaria, Anthemis, Galinsoga, Chenopodium, Urtica,Senecio, Amaranthus, Portulaca, Xanthium, Convolvulus, Ipomoea,Polygonum, Sesbania, Ambrosia, Cirsium, Carduus, Sonchus, Solanum,Rorippa, Rotala, Lindernia, Lamium, Veronica, Abutilon, Emex, Datura,Viola, Galeopsis, Papaver, Centaurea, Trifolium, Ranunculus, andTaraxacum. Monocotyledonous weeds include, but are not limited to, weedsof of the genera: Echinochloa, Setaria, Panicum, Digitaria, Phleum, Poa,Festuca, Eleusine, Brachiaria, Lolium, Bromus, Avena, Cyperus, Sorghum,Agropyron, Cynodon, Monochoria, Fimbristyslis, Sagittaria, Eleocharis,Scirpus, Paspalum, Ischaemum, Sphenoclea, Dactyloctenium, Agrostis,Alopecurus, and Apera. In addition, the weeds of the present inventioncan include, for example, crop plants that are growing in an undesiredlocation. For example, a volunteer maize plant that is in a field thatpredominantly comprises soybean plants can be considered a weed, if themaize plant is undesired in the field of soybean plants.

The term “plant” is used in its broadest sense as it pertains to organicmaterial and is intended to encompass eukaryotic organisms that aremembers of the Kingdom Plantae, examples of which include but are notlimited to vascular plants, vegetables, grains, flowers, trees, herbs,bushes, grasses, vines, ferns, mosses, fungi and algae, etc, as well asclones, offsets, and parts of plants used for asexual propagation (e.g.cuttings, pipings, shoots, rhizomes, underground stems, clumps, crowns,bulbs, corms, tubers, rhizomes, plants/tissues produced in tissueculture, etc.). The term “plant” further encompasses whole plants,ancestors and progeny of the plants and plant parts, including seeds,shoots, stems, leaves, roots (including tubers), flowers, florets,fruits, pedicles, peduncles, stamen, anther, stigma, style, ovary,petal, sepal, carpel, root tip, root cap, root hair, leaf hair, seedhair, pollen grain, microspore, cotyledon, hypocotyl, epicotyl, xylem,phloem, parenchyma, endosperm, a companion cell, a guard cell, and anyother known organs, tissues, and cells of a plant, and tissues andorgans, wherein each of the aforementioned comprise the gene/nucleicacid of interest. The term “plant” also encompasses plant cells,suspension cultures, callus tissue, embryos, meristematic regions,gametophytes, sporophytes, pollen and microspores, again wherein each ofthe aforementioned comprises the gene/nucleic acid of interest.

Plants that are particularly useful in the methods of the inventioninclude all plants which belong to the superfamily Viridiplantae, inparticular monocotyledonous and dicotyledonous plants including fodderor forage legumes, ornamental plants, food crops, trees or shrubsselected from the list comprising Acer spp., Actinidia spp., Abelmoschusspp., Agave sisalana, Agropyron spp., Agrostis stolonifera, Allium spp.,Amaranthus spp., Ammophila arenaria, Ananas comosus, Annona spp., Apiumgraveolens, Arachis spp, Artocarpus spp., Asparagus officinalis, Avenaspp. (e.g. Avena sativa, Avena fatua, Avena byzantina, Avena fatua var.sativa, Avena hybrida), Averrhoa carambola, Bambusa sp., Benincasahispida, Bertholletia excelsea, Beta vulgaris, Brassica spp. (e.g.Brassica napus, Brassica rapa ssp. [canola, oilseed rape, turnip rape]),Cadaba farinosa, Camellia sinensis, Canna indica, Cannabis sativa,Capsicum spp., Carex elata, Carica papaya, Carissa macrocarpa, Caryaspp., Carthamus tinctorius, Castanea spp., Ceiba pentandra, Cichoriumendivia, Cinnamomum spp., Citrullus lanatus, Citrus spp., Cocos spp.,Coffea spp., Colocasia esculenta, Cola spp., Corchorus sp., Coriandrumsativum, Corylus spp., Crataegus spp., Crocus sativus, Cucurbita spp.,Cucumis spp., Cynara spp., Daucus carota, Desmodium spp., Dimocarpuslongan, Dioscorea spp., Diospyros spp., Echinochloa spp., Elaeis (e.g.Elaeis guineensis, Elaeis oleifera), Eleusine coracana, Eragrostis tef,Erianthus sp., Eriobotrya japonica, Eucalyptus sp., Eugenia uniflora,Fagopyrum spp., Fagus spp., Festuca arundinacea, Ficus carica,Fortunella spp., Fragaria spp., Ginkgo biloba, Glycine spp. (e.g.Glycine max, Soja hispida or Soja max), Gossypium hirsutum, Helianthusspp. (e.g. Helianthus annuus), Hemerocallis fulva, Hibiscus spp.,Hordeum spp. (e.g. Hordeum vulgare), Ipomoea batatas, Juglans spp.,Lactuca sativa, Lathyrus spp., Lens culinaris, Linum usitatissimum,Litchi chinensis, Lotus spp., Luffa acutangula, Lupinus spp., Luzulasylvatica, Lycopersicon spp. (e.g. Lycopersicon esculentum, Lycopersiconlycopersicum, Lycopersicon pyriforme), Macrotyloma spp., Malus spp.,Malpighia emarginata, Mammea americana, Mangifera indica, Manihot spp.,Manilkara zapota, Medicago sativa, Melilotus spp., Mentha spp.,Miscanthus sinensis, Momordica spp., Morus nigra, Musa spp., Nicotianaspp., Olea spp., Opuntia spp., Ornithopus spp., Oryza spp. (e.g. Oryzasativa, Oryza latifolia), Panicum miliaceum, Panicum virgatum,Passiflora edulis, Pastinaca sativa, Pennisetum sp., Persea spp.,Petroselinum crispum, Phalaris arundinacea, Phaseolus spp., Phleumpratense, Phoenix spp., Phragmites australis, Physalis spp., Pinus spp.,Pistacia vera, Pisum spp., Poa spp., Populus spp., Prosopis spp., Prunusspp., Psidium spp., Punica granatum, Pyrus communis, Quercus spp.,Raphanus sativus, Rheum rhabarbarum, Ribes spp., Ricinus communis, Rubusspp., Saccharum spp., Salix sp., Sambucus spp., Secale cereale, Sesamumspp., Sinapis sp., Solanum spp. (e.g. Solanum tuberosum, Solanumintegrifolium or Solanum lycopersicum), Sorghum bicolor, Spinacia spp.,Syzygium spp., Tagetes spp., Tamarindus indica, Theobroma cacao,Trifolium spp., Tripsacum dactyloides, Triticosecale rimpaui, Triticumspp. (e.g. Triticum aestivum, Triticum durum, Triticum turgidum,Triticum hybernum, Triticum macha, Triticum sativum, Triticum monococcumor Triticum vulgare), Tropaeolum minus, Tropaeolum majus, Vacciniumspp., Vicia spp., Vigna spp., Viola odorata, Vitis spp., Zea mays,Zizania palustris, Ziziphus spp., amaranth, artichoke, asparagus,broccoli, Brussels sprouts, cabbage, canola, carrot, cauliflower,celery, collard greens, flax, kale, lentil, oilseed rape, okra, onion,potato, rice, soybean, strawberry, sugar beet, sugar cane, sunflower,tomato, squash, tea and algae, amongst others. According to a preferredembodiment of the present invention, the plant is a crop plant. Examplesof crop plants include inter alia soybean, sunflower, canola, alfalfa,rapeseed, cotton, tomato, potato or tobacco. Further preferebly, theplant is a monocotyledonous plant, such as sugarcane. Furtherpreferably, the plant is a cereal, such as rice, maize, wheat, barley,millet, rye, sorghum or oats.

Generally, the term “herbicide” is used herein to mean an activeingredient that kills, controls or otherwise adversely modifies thegrowth of plants. The preferred amount or concentration of the herbicideis an “effective amount” or “effective concentration.” By “effectiveamount” and “effective concentration” is intended an amount andconcentration, respectively, that is sufficient to kill or inhibit thegrowth of a similar, wild-type, plant, plant tissue, plant cell, or hostcell, but that said amount does not kill or inhibit as severely thegrowth of the herbicide-resistant plants, plant tissues, plant cells,and host cells of the present invention. Typically, the effective amountof a herbicide is an amount that is routinely used in agriculturalproduction systems to kill weeds of interest. Such an amount is known tothose of ordinary skill in the art. Herbicidal activity is exhibited byherbicides useful for the the present invention when they are applieddirectly to the plant or to the locus of the plant at any stage ofgrowth or before planting or emergence. The effect observed depends uponthe plant species to be controlled, the stage of growth of the plant,the application parameters of dilution and spray drop size, the particlesize of solid components, the environmental conditions at the time ofuse, the specific compound employed, the specific adjuvants and carriersemployed, the soil type, and the like, as well as the amount of chemicalapplied. These and other factors can be adjusted as is known in the artto promote non-selective or selective herbicidal action. Generally, itis preferred to apply the herbicide postemergence to relatively immatureundesirable vegetation to achieve the maximum control of weeds.

By a “herbicide-tolerant” or “herbicide-resistant” plant, it is intendedthat a plant that is tolerant or resistant to at least one herbicide ata level that would normally kill, or inhibit the growth of, a normal orwild-type plant. Levels of herbicide that normally inhibit growth of anon-tolerant plant are known and readily determined by those skilled inthe art. Examples include the amounts recommended by manufacturers forapplication. The maximum rate is an example of an amount of herbicidethat would normally inhibit growth of a non-tolerant plant. For thepresent invention, the terms “herbicide-tolerant” and“herbicide-resistant” are used interchangeably and are intended to havean equivalent meaning and an equivalent scope. Similarly, the terms“herbicide-tolerance” and “herbicide-resistance” are usedinterchangeably and are intended to have an equivalent meaning and anequivalent scope. Similarly, the terms “tolerant” and “resistant” areused interchangeably and are intended to have an equivalent meaning andan equivalent scope. As used herein, in regard to an herbicidalcomposition useful in various embodiments hereof, terms such asCESA-inhibiting herbicides, and the like, refer to those agronomicallyacceptable herbicide active ingredients (A.I.) recognized in the art.Similarly, terms such as fungicide, nematicide, pesticide, and the like,refer to other agronomically acceptable active ingredients recognized inthe art.

When used in reference to a particular mutant enzyme or polypeptide,terms such as herbicide-tolerant and herbicide-tolerance refer to theability of such enzyme or polypeptide to perform its physiologicalactivity in the presence of an amount of an herbicide A.I. that wouldnormally inactivate or inhibit the activity of the wild-type(non-mutant) version of said enzyme or polypeptide. For example, whenused specifically in regard to a CESA enzyme, it refers specifically tothe ability to tolerate a CESA-inhibitor. By “herbicide-tolerantwildtype or mutated CESA protein” or “herbicide-resistant wildtype ormutated CESA protein”, it is intended that such a CESA protein displayshigher CESA activity, relative to the CESA activity of a wild-type CESAprotein, when in the presence of at least one herbicide that is known tointerfere with CESA activity and at a concentration or level of theherbicide that is known to inhibit the CESA activity of the wild-typeCESA protein. Furthermore, the CESA activity of such aherbicide-tolerant or herbicide-resistant wildtype or mutated CESAprotein may be referred to herein as “herbicide-tolerant” or“herbicide-resistant” CESA activity.

As used herein, “recombinant,” when referring to nucleic acid orpolypeptide, indicates that such material has been altered as a resultof human application of a recombinant technique, such as bypolynucleotide restriction and ligation, by polynucleotideoverlap-extension, or by genomic insertion or transformation. A genesequence open reading frame is recombinant if that nucleotide sequencehas been removed from it natural text and cloned into any type ofartificial nucleic acid vector. The term recombinant also can refer toan organism having a recombinant material, e.g., a plant that comprisesa recombinant nucleic acid can be considered a recombinant plant.

The term “transgenic plant” refers to a plant that comprises aheterologous polynucleotide. Preferably, the heterologous polynucleotideis stably integrated within the genome such that the polynucleotide ispassed on to successive generations. The heterologous polynucleotide maybe integrated into the genome alone or as part of a recombinantexpression cassette. “Transgenic” is used herein to refer to any cell,cell line, callus, tissue, plant part or plant, the genotype of whichhas been so altered by the presence of heterologous nucleic acidincluding those transgenic organisms or cells initially so altered, aswell as those created by crosses or asexual propagation from the initialtransgenic organism or cell. In some embodiments, a “recombinant”organism is a “transgenic” organism. The term “transgenic” as usedherein is not intended to encompass the alteration of the genome(chromosomal or extra-chromosomal) by conventional plant breedingmethods (e.g., crosses) or by naturally occurring events such as, e.g.,self-fertilization, random cross-fertilization, non-recombinant viralinfection, non-recombinant bacterial transformation, non-recombinanttransposition, or spontaneous mutation.

As used herein, “mutagenized” refers to an organism or DNA thereofhaving alteration(s) in the biomolecular sequence of its native geneticmaterial as compared to the sequence of the genetic material of acorresponding wild-type organism or DNA, wherein the alteration(s) ingenetic material were induced and/or selected by human action. Examplesof human action that can be used to produce a mutagenized organism orDNA include, but are not limited to, as illustrated in regard toherbicide tolerance: tissue culture of plant cells (e.g., calli) andselection thereof with herbicides (e.g., CESA-inhibiting herbicides),treatment of plant cells with a chemical mutagen such as EMS andsubsequent selection with herbicide(s); or by treatment of plant cellswith x-rays and subsequent selection with herbicide(s). Any method knownin the art can be used to induce mutations. Methods of inducingmutations can induce mutations in random positions in the geneticmaterial or can induce mutations in specific locations in the geneticmaterial (i.e., can be directed mutagenesis techniques), such as by useof a genoplasty technique.

As used herein, a “genetically modified organism” (GMO) is an organismwhose genetic characteristics contain alteration(s) that were producedby human effort causing transfection that results in transformation of atarget organism with genetic material from another or “source” organism,or with synthetic or modified-native genetic material, or an organismthat is a descendant thereof that retains the inserted genetic material.The source organism can be of a different type of organism (e.g., a GMOplant can contain bacterial genetic material) or from the same type oforganism (e.g., a GMO plant can contain genetic material from anotherplant). As used herein in regard to plants and other organisms,“recombinant,” “transgenic,” and “GMO” are considered synonyms andindicate the presence of genetic material from a different source; incontrast, “mutagenized” is used to refer to a plant or other organism,or the DNA thereof, in which no such transgenic material is present, butin which the native genetic material has become mutated so as to differfrom a corresponding wild-type organism or DNA.

As used herein, “wild-type” or “corresponding wild-type plant” means thetypical form of an organism or its genetic material, as it normallyoccurs, as distinguished from, e.g., mutagenized and/or recombinantforms. Similarly, by “control cell” or “similar, wild-type, plant, planttissue, plant cell or host cell” is intended a plant, plant tissue,plant cell, or host cell, respectively, that lacks theherbicide-resistance characteristics and/or particular polynucleotide ofthe invention that are disclosed herein. The use of the term “wild-type”is not, therefore, intended to imply that a plant, plant tissue, plantcell, or other host cell lacks recombinant DNA in its genome, and/ordoes not possess herbicide-resistant characteristics that are differentfrom those disclosed herein.

As used herein, “descendant” refers to any generation plant. In someembodiments, a descendant is a first, second, third, fourth, fifth,sixth, seventh, eight, ninth, or tenth generation plant.

As used herein, “progeny” refers to a first generation plant.

The term “seed” comprises seeds of all types, such as, for example, trueseeds, caryopses, achenes, fruits, tubers, seedlings and similar forms.In the context of Brassica and Sinapis species, “seed” refers to trueseed(s) unless otherwise specified. For example, the seed can be seed oftransgenic plants or plants obtained by traditional breeding methods.Examples of traditional breeding methods can include cross-breeding,selfing, backcrossing, embryo rescue, in-crossing, out-crossing,inbreeding, selection, asexual propagation, and other traditionaltechniques as are known in the art.

Although exemplified with reference to specific plants or plantvarieties and their hybrids, in various embodiments, the presentlydescribed methods using CESA-inhibiting herbicides can be employed witha variety of commercially valuable plants. CESA-inhibitingherbicides-tolerant plant lines described as useful herein can beemployed in weed control methods either directly or indirectly, i.e.either as crops for herbicide treatment or as CESA-inhibitingherbicides-tolerance trait donor lines for development, as bytraditional plant breeding, to produce other varietal and/or hybridcrops containing such trait or traits. All such resulting variety orhybrids crops, containing the ancestral CESA-inhibitingherbicides-tolerance trait or traits can be referred to herein asprogeny or descendant of the ancestral, CESA-inhibitingherbicides-tolerant line(s). Such resulting plants can be said to retainthe “herbicide tolerance characteristic(s)” of the ancestral plant, i.e.meaning that they possess and express the ancestral genetic molecularcomponents responsible for the trait.

In one aspect, the present invention provides a plant or plant partcomprising a polynucleotide encoding a wildtype or mutated CESApolypeptide, the expression of said polynucleotide confers to the plantor plant part tolerance to CESA-inhibiting herbicides.

In a preferred embodiment, the plant has been previously produced by aprocess comprising recombinantly preparing a plant by introducing andover-expressing a wildtype or mutated CESA transgene according to thepresent invention, as described in greater detail hereinafter.

In another preferred embodiment, the plant has been previously producedby a process comprising in situ mutagenizing plant cells or seeds, toobtain plant cells or plants which express a wildtype or mutated CESA.

In another embodiment, the polynucleotide encoding the wildtype ormutated CESA polypeptide polypeptide comprises the nucleic acid sequenceset forth in SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76,or 77, or a variant or derivative thereof.

In other embodiments, the wildtype or mutated CESA polypeptide for useaccording to the present invention is a functional variant having, overthe full-length of the variant, at least about 80%, illustratively, atleast about 80%, 90%, 95%, 98%, to, 99% or more amino acid sequenceidentity to SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or 64.

In another embodiment, the wildtype or mutated CESA polypeptide for useaccording to the present invention is a functional fragment of apolypeptide having the amino acid sequence set forth in SEQ ID NO: 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, or 64.

It is recognized that the CESA polynucleotide molecules and CESApolypeptides of the invention encompass polynucleotide molecules andpolypeptides comprising a nucleotide or an amino acid sequence that issufficiently identical to nucleotide sequences set forth in SEQ ID Nos:65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, or 77, or to the aminoacid sequences set forth in SEQ ID Nos: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46,47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or64. The term “sufficiently identical” is used herein to refer to a firstamino acid or nucleotide sequence that contains a sufficient or minimumnumber of identical or equivalent (e.g., with a similar side chain)amino acid residues or nucleotides to a second amino acid or nucleotidesequence such that the first and second amino acid or nucleotidesequences have a common structural domain and/or common functionalactivity.

Generally, “sequence identity” refers to the extent to which twooptimally aligned DNA or amino acid sequences are invariant throughout awindow of alignment of components, e.g., nucleotides or amino acids. An“identity fraction” for aligned segments of a test sequence and areference sequence is the number of identical components that are sharedby the two aligned sequences divided by the total number of componentsin reference sequence segment, i.e., the entire reference sequence or asmaller defined part of the reference sequence. “Percent identity” isthe identity fraction times 100. Optimal alignment of sequences foraligning a comparison window are well known to those skilled in the artand may be conducted by tools such as the local homology algorithm ofSmith and Waterman, the homology alignment algorithm of Needleman andWunsch, the search for similarity method of Pearson and Lipman, andpreferably by computerized implementations of these algorithms such asGAP, BESTFIT, FASTA, and TFASTA available as part of the GCG. WisconsinPackage. (Accelrys Inc. Burlington, Mass.)

Polynucleotides and Oligonucleotides

By an “isolated polynucleotide”, including DNA, RNA, or a combination ofthese, single or double stranded, in the sense or antisense orientationor a combination of both, dsRNA or otherwise, we mean a polynucleotidewhich is at least partially separated from the polynucleotide sequenceswith which it is associated or linked in its native state. Preferably,the isolated polynucleotide is at least 60% free, preferably at least75% free, and most preferably at least 90% free from other componentswith which they are naturally associated. As the skilled addressee wouldbe aware, an isolated polynucleotide can be an exogenous polynucleotidepresent in, for example, a transgenic organism which does not naturallycomprise the polynucleotide. Furthermore, the terms “polynucleotide(s)”,“nucleic acid sequence(s)”, “nucleotide sequence(s)”, “nucleic acid(s)”,“nucleic acid molecule” are used interchangeably herein and refer tonucleotides, either ribonucleotides or deoxyribonucleotides or acombination of both, in a polymeric unbranched form of any length.

The term “mutated CESA nucleic acid” refers to a CESA nucleic acidhaving a sequence that is mutated from a wild-type CESA nucleic acid andthat confers increased CESA-inhibiting herbicide tolerance to a plant inwhich it is expressed. Furthermore, the term “mutated cellulose synthase(mutated CESA)” refers to the replacement of an amino acid of thewild-type primary sequences of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46,47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or64, or a variant, a derivative, a homologue, an orthologue, or paraloguethereof, with another amino acid. The expression “mutated amino acid”will be used below to designate the amino acid which is replaced byanother amino acid, thereby designating the site of the mutation in theprimary sequence of the protein.

In a preferred embodiment, the CESA nucleotide sequence encoding amutated CESA comprises the sequence of SEQ ID NO: 65, 66, 67, 68, 69,70, 71, 72, 73, 74, 75, 76, or 77, or a variant or derivative thereof

Furthermore, it will be understood by the person skilled in the art thatthe CESA nucleotide sequences encompasse homologues, paralogues and andorthologues of SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,76, or 77, as defined hereinafter.

The term “variant” with respect to a sequence (e.g., a polypeptide ornucleic acid sequence such as—for example—a transcription regulatingnucleotide sequence of the invention) is intended to mean substantiallysimilar sequences. For nucleotide sequences comprising an open readingframe, variants include those sequences that, because of the degeneracyof the genetic code, encode the identical amino acid sequence of thenative protein. Naturally occurring allelic variants such as these canbe identified with the use of well-known molecular biology techniques,as, for example, with polymerase chain reaction (PCR) and hybridizationtechniques. Variant nucleotide sequences also include syntheticallyderived nucleotide sequences, such as those generated, for example, byusing site-directed mutagenesis and for open reading frames, encode thenative protein comprising the sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, or 64, as well as those that encode a polypeptide having aminoacid substitutions relative to the native protein, e.g. the mutated CESAaccording to the present invention as disclosed herein. Generally,nucleotide sequence variants of the invention will have at least 30, 40,50, 60, to 70%, e.g., preferably 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%,to 79%, generally at least 80%, e.g., 81%-84%, at least 85%, e.g., 86%,87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, to 98% and 99%nucleotide “sequence identity” to the nucleotide sequence of SEQ ID NO:65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, or 77. The % identity ofa polynucleotide is determined by GAP (Needleman and Wunsch, 1970)analysis (GCG program) with a gap creation penalty=5, and a gapextension penalty=0.3. Unless stated otherwise, the query sequence is atleast 45 nucleotides in length, and the GAP analysis aligns the twosequences over a region of at least 45 nucleotides. Preferably, thequery sequence is at least 150 nucleotides in length, and the GAPanalysis aligns the two sequences over a region of at least 150nucleotides. More preferably, the query sequence is at least 300nucleotides in length and the GAP analysis aligns the two sequences overa region of at least 300 nucleotides. Even more preferably, the GAPanalysis aligns the two sequences over their entire length.

Polypeptides

By “substantially purified polypeptide” or “purified” a polypeptide ismeant that has been separated from one or more lipids, nucleic acids,other polypeptides, or other contaminating molecules with which it isassociated in its native state. It is preferred that the substantiallypurified polypeptide is at least 60% free, more preferably at least 75%free, and more preferably at least 90% free from other components withwhich it is naturally associated. As the skilled addressee willappreciate, the purified polypeptide can be a recombinantly producedpolypeptide. The terms “polypeptide” and “protein” are generally usedinterchangeably and refer to a single polypeptide chain which may or maynot be modified by addition of non-amino acid groups. It would beunderstood that such polypeptide chains may associate with otherpolypeptides or proteins or other molecules such as co-factors. Theterms “proteins” and “polypeptides” as used herein also includevariants, mutants, modifications, analogous and/or derivatives of thepolypeptides of the invention as described herein.

The % identity of a polypeptide is determined by GAP (Needleman andWunsch, 1970) analysis (GCG program) with a gap creation penalty=5, anda gap extension penalty=0.3. The query sequence is at least 25 aminoacids in length, and the GAP analysis aligns the two sequences over aregion of at least 25 amino acids. More preferably, the query sequenceis at least 50 amino acids in length, and the GAP analysis aligns thetwo sequences over a region of at least 50 amino acids. More preferably,the query sequence is at least 100 amino acids in length and the GAPanalysis aligns the two sequences over a region of at least 100 aminoacids. Even more preferably, the query sequence is at least 250 aminoacids in length and the GAP analysis aligns the two sequences over aregion of at least 250 amino acids. Even more preferably, the GAPanalysis aligns the two sequences over their entire length.

With regard to a defined polypeptide, it will be appreciated that %identity figures higher than those provided above will encompasspreferred embodiments. Thus, where applicable, in light of the minimum %identity figures, it is preferred that the CESA polypeptide of theinvention comprises an amino acid sequence which is at least 40%, morepreferably at least 45%, more preferably at least 50%, more preferablyat least 55%, more preferably at least 60%, more preferably at least65%, more preferably at least 70%, more preferably at least 75%, morepreferably at least 80%, more preferably at least 85%, more preferablyat least 90%, more preferably at least 91%, more preferably at least92%, more preferably at least 93%, more preferably at least 94%, morepreferably at least 95%, more preferably at least 96%, more preferablyat least 97%, more preferably at least 98%, more preferably at least99%, more preferably at least 99.1%, more preferably at least 99.2%,more preferably at least 99.3%, more preferably at least 99.4%, morepreferably at least 99.5%, more preferably at least 99.6%, morepreferably at least 99.7%, more preferably at least 99.8%, and even morepreferably at least 99.9% identical to SEQ ID NO: 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, or 64.

By “variant” polypeptide is intended a polypeptide derived from theprotein of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or 64, by deletion(so-called truncation) or addition of one or more amino acids to theN-terminal and/or C-terminal end of the native protein; deletion oraddition of one or more amino acids at one or more sites in the nativeprotein; or substitution of one or more amino acids at one or more sitesin the native protein. Such variants may result from, for example,genetic polymorphism or from human manipulation. Methods for suchmanipulations are generally known in the art.

“Derivatives” of a protein encompass peptides, oligopeptides,polypeptides, proteins and enzymes having amino acid substitutions,deletions and/or insertions relative to the unmodified protein inquestion and having similar biological and functional activity as theunmodified protein from which they are derived. Thus, functionalvariants and fragments of the CESA polypeptides, and nucleic acidmolecules encoding them, also are within the scope of the presentinvention, and unless specifically described otherwise, irrespective ofthe origin of said polypeptide and irrespective of whether it occursnaturally. Various assays for functionality of a CESA polypeptide can beemployed. For example, a functional variant or fragment of the CESApolypeptide can be assayed to determine its ability to conferCESA-inhibiting herbicides tolerance. By way of illustration, aCESA-inhibiting herbicides tolerance can be defined as insensitivity toCESA inhibiting herbicides sufficient to provide a determinable increasein tolerance to CESA-inhibiting herbicides in a plant or plant partcomprising a recombinant polynucleotide encoding the variant or fragmentof the CESA polypeptide, wherein the plant or plant part expresses thevariant or fragment at up to about 0.5%, illustratively, about 0.05 toabout 0.5%, about 0.1 to about 0.4%, and about 0.2 to about 0.3%, of thetotal cellular protein relative to a similarly treated control plantthat does not express the variant or fragment.

In a preferred embodiment, the mutated CESA polypeptide is a functionalvariant or fragment of a cellulose synthase having the amino acidsequence set forth in SEQ ID NO: 1 or 3, wherein the functional variantor fragment has at least about 80% amino acid sequence identity to SEQID NO:1 or 3.

In other embodiments, the functional variant or fragment further has aCESA-inhibiting herbicides tolerance defined as insensitivity to CESAinhibiting herbicides sufficient to provide a determinable increase intolerance to CESA-inhibiting herbicides in a plant or plant partcomprising a recombinant polynucleotide encoding the variant orfragment, wherein the plant or plant part expresses the variant orfragment at up to about 0.5% of the total cellular protein to asimilarly treated control plant that does not express the variant orfragment.

“Homologues” of a protein encompass peptides, oligopeptides,polypeptides, proteins and enzymes having amino acid substitutions,deletions and/or insertions relative to the unmodified protein inquestion and having similar biological and functional activity as theunmodified protein from which they are derived.

In addition, one of ordinary skill in the art will further appreciatethat changes can be introduced by mutation into the nucleotide sequencesof the invention thereby leading to changes in the amino acid sequenceof the encoded proteins without altering the biological activity of theproteins. Thus, for example, an isolated polynucleotide moleculeencoding a mutated CESA polypeptide having an amino acid sequence thatdiffers from that of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or 64, canbe created by introducing one or more nucleotide substitutions,additions, or deletions into the corresponding nucleotide sequence, suchthat one or more amino acid substitutions, additions or deletions areintroduced into the encoded protein. Mutations can be introduced bystandard techniques, such as site-directed mutagenesis and PCR-mediatedmutagenesis. Such variant nucleotide sequences are also encompassed bythe present invention. For example, preferably, conservative amino acidsubstitutions may be made at one or more predicted preferablynonessential amino acid residues. A “nonessential” amino acid residue isa residue that can be altered from the wild-type sequence of a proteinwithout altering the biological activity, whereas an “essential” aminoacid residue is required for biological activity.

A deletion refers to removal of one or more amino acids from a protein.

An insertion refers to one or more amino acid residues being introducedinto a predetermined site in a protein. Insertions may compriseN-terminal and/or C-terminal fusions as well as intra-sequenceinsertions of single or multiple amino acids. Generally, insertionswithin the amino acid sequence will be smaller than N- or C-terminalfusions, of the order of about 1 to 10 residues. Examples of N- orC-terminal fusion proteins or peptides include the binding domain oractivation domain of a transcriptional activator as used in the yeasttwo-hybrid system, phage coat proteins, (histidine)-6-tag, glutathioneS-transferase-tag, protein A, maltose-binding protein, dihydrofolatereductase, Tag·100 epitope, c-myc epitope, FLAG®-epitope, lacZ, CMP(calmodulin-binding peptide), HA epitope, protein C epitope and VSVepitope.

A substitution refers to replacement of amino acids of the protein withother amino acids having similar properties (such as similarhydrophobicity, hydrophilicity, antigenicity, propensity to form orbreak α-helical structures or β-sheet structures). Amino acidsubstitutions are typically of single residues, but may be clustereddepending upon functional constraints placed upon the polypeptide andmay range from 1 to 10 amino acids; insertions will usually be of theorder of about 1 to 10 amino acid residues. A conservative amino acidsubstitution is one in which the amino acid residue is replaced with anamino acid residue having a similar side chain. Families of amino acidresidues having similar side chains have been defined in the art. Thesefamilies include amino acids with basic side chains (e.g., lysine,arginine, histidine), acidic side chains (e.g., aspartic acid, glutamicacid), uncharged polar side chains (e.g., glycine, asparagine,glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains(e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine,methionine, tryptophan), beta-branched side chains (e.g., threonine,valine, isoleucine) and aromatic side chains (e.g., tyrosine,phenylalanine, tryptophan, histidine). Such substitutions would not bemade for conserved amino acid residues, or for amino acid residuesresiding within a conserved motif. Conservative substitution tables arewell known in the art (see for example Creighton (1984) Proteins. W.H.Freeman and Company (Eds).

Amino acid substitutions, deletions and/or insertions may readily bemade using peptide synthetic techniques well known in the art, such assolid phase peptide synthesis and the like, or by recombinant DNAmanipulation. Methods for the manipulation of DNA sequences to producesubstitution, insertion or deletion variants of a protein are well knownin the art. For example, techniques for making substitution mutations atpredetermined sites in DNA are well known to those skilled in the artand include M13 mutagenesis, T7-Gen in vitro mutagenesis (USB,Cleveland, Ohio), QuickChange Site Directed mutagenesis (Stratagene, SanDiego, Calif.), PCR-mediated site-directed mutagenesis or othersite-directed mutagenesis protocols.

“Derivatives” further include peptides, oligopeptides, polypeptideswhich may, compared to the amino acid sequence of thenaturally-occurring form of the protein, such as the protein ofinterest, comprise substitutions of amino acids with non-naturallyoccurring amino acid residues, or additions of non-naturally occurringamino acid residues. “Derivatives” of a protein also encompass peptides,oligopeptides, polypeptides which comprise naturally occurring altered(glycosylated, acylated, prenylated, phosphorylated, myristoylated,sulphated etc.) or non-naturally altered amino acid residues compared tothe amino acid sequence of a naturally-occurring form of thepolypeptide. A derivative may also comprise one or more non-amino acidsubstituents or additions compared to the amino acid sequence from whichit is derived, for example a reporter molecule or other ligand,covalently or non-covalently bound to the amino acid sequence, such as areporter molecule which is bound to facilitate its detection, andnon-naturally occurring amino acid residues relative to the amino acidsequence of a naturally-occurring protein. Furthermore, “derivatives”also include fusions of the naturally-occurring form of the protein withtagging peptides such as FLAG, HIS6 or thioredoxin (for a review oftagging peptides, see Terpe, Appl. Microbiol. Biotechnol. 60, 523-533,2003).

“Orthologues” and “paralogues” encompass evolutionary concepts used todescribe the ancestral relationships of genes. Paralogues are geneswithin the same species that have originated through duplication of anancestral gene; orthologues are genes from different organisms that haveoriginated through speciation, and are also derived from a commonancestral gene. A non-limiting list of examples of such orthologues isshown in Table 1. It will be understood by the person skilled in the artthat the sequences of SEQ ID NOs: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or 64, aslisted in Table 1 represent orthologues and paralogues to SEQ ID NO:1.

It is well-known in the art that paralogues and orthologues may sharedistinct domains harboring suitable amino acid residues at given sites,such as binding pockets for particular substrates or binding motifs forinteraction with other proteins.

The term “domain” refers to a set of amino acids conserved at specificpositions along an alignment of sequences of evolutionarily relatedproteins. While amino acids at other positions can vary betweenhomologues, amino acids that are highly conserved at specific positionsindicate amino acids that are likely essential in the structure,stability or function of a protein. Identified by their high degree ofconservation in aligned sequences of a family of protein homologues,they can be used as identifiers to determine if any polypeptide inquestion belongs to a previously identified polypeptide family.

The term “motif” or “consensus sequence” refers to a short conservedregion in the sequence of evolutionarily related proteins. Motifs arefrequently highly conserved parts of domains, but may also include onlypart of the domain, or be located outside of conserved domain (if all ofthe amino acids of the motif fall outside of a defined domain).

In a preferred embodiment, the CESA polypeptide useful for the presentinvention, comprises one or more of the following motifs:

-   -   i) Motif 1a:

(SEQ ID NO: 78) [V/I][A/V]G[V/I/F][S/T][Y/D/N/A]A[V/I/L][N/S/G][S/N]G[Y/F/E][Q/D/G/E/H][S/A]WG[P/A]L[F/M/L]G [K/R][L/V][F/L]F.

-   -   -   Preferably said motif is

(motif 1b; SEQ ID NO: 79)[V/I]AG[V/I]S[Y/D/N]A[V/I][N/S][S/N]G[Y/F][Q/D]SWGPL[F/M/L]G[K/R]L[F/L]F.

-   -   -   More preferably said motif is

(motif 1c; SEQ ID NO: 80) VAG[V/I]SYA[V/I]NSGYQSWGPL[F/M]GKL[F/L]F

-   -   ii) Motif 2a:

(SEQ ID NO: 81) [V/L/I]W[S/A][V/A/I]LL[A/S]S[I/F/V][F/L][S/T][L/V][L/M/V/I]WV[R/K][I/V][N/D]PF

-   -   -   Preferably, said motif is

(motif 2b; SEQ ID NO: 82)VW[S/A][V/A/I]LL[A/S]S[I/F][F/L][S/T][L/V][L/M]WV [R/K][I/V][N/D]PF;

-   -   -   More preferably said motif is

(motif 2c; SEQ ID NO: 83) VW[S/A][V/A/I]LLASIFSL[L/M]WV[R/K]I[N/D]PF

Motifs 1a-c, 2a-c, given above were derived using the ClustalW algorithmto generate the alignments of cellulose synthase sequences (FIG. 2 A-C)(Larkin et al., Bioinformatics 23:21 (2007) 2947-2948 pp. 28-36). Themotifs were essentially derived based on sequence alignment; highlyconserved regions were identified that contain the site of mutationsconferring azine-herbicide tolerance. Residues within square bracketsrepresent alternatives.

In a preferred embodiment, a CESA polypeptide as applied hereincomprises, at least 1, at least 2, selected from the group comprisingmotifs 1a, 2a, as given above. Alternatively or in addition, in anotherpreferred embodiment, a CESA polypeptide as applied herein comprises atleast 1, at least 2, motifs selected from the group comprising motifs1b, 2b, as given above. Alternatively or in addition, in anotherpreferred embodiment, a CESA polypeptide as applied herein comprises atleast 1, at least 2, motifs selected from the group comprising motifs1c, 2c, as given above.

Additionally or alternatively, the homologue of a CESA protein has inincreasing order of preference at least 20%, 21%, 22%, 23%, 24%, 25%,26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%,40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%,54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%,68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%,82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,96%, 97%, 98%, or 99% overall sequence identity to the amino acidrepresented by SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or 64, provided thatthe homologous protein comprises any one or more of the conserved motifs1 and/or 2 as outlined above. The overall sequence identity isdetermined using a global alignment algorithm, such as the NeedlemanWunsch algorithm in the program GAP (GCG Wisconsin Package, Accelrys),preferably with default parameters and preferably with sequences ofmature proteins (i.e. without taking into account secretion signals ortransit peptides). Compared to overall sequence identity, the sequenceidentity will generally be higher when only conserved domains or motifsare considered. Preferably the motifs in a CESA polypeptide have, inincreasing order of preference, at least 70%, 71%, 72%, 73%, 74%, 75%,76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity toany one or more of the motifs represented by SEQ ID NO: 78, 79, 80, 81,82, and 83 (Motifs 1a, 1b, 1c, 2a, 2b, 2c).

Specialist databases exist for the identification of domains, forexample, SMART (Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95,5857-5864; Letunic et al. (2002) Nucleic Acids Res 30, 242-244),InterPro (Mulder et al., (2003) Nucl. Acids. Res. 31, 315-318), Prosite(Bucher and Bairoch (1994), A generalized profile syntax forbiomolecular sequences motifs and its function in automatic sequenceinterpretation. (In) ISMB-94; Proceedings 2nd International Conferenceon Intelligent Systems for Molecular Biology. Altman R., Brutlag D.,Karp P., Lathrop R., Searls D., Eds., pp 53-61, AAAI Press, Menlo Park;Hulo et al., Nucl. Acids. Res. 32:D134-D137, (2004)), or Pfam (Batemanet al., Nucleic Acids Research 30(1): 276-280 (2002)). A set of toolsfor in silico analysis of protein sequences is available on the ExPASyproteomics server (Swiss Institute of Bioinformatics (Gasteiger et al.,ExPASy: the proteomics server for in-depth protein knowledge andanalysis, Nucleic Acids Res. 31:3784-3788(2003)). Domains or motifs mayalso be identified using routine techniques, such as by sequencealignment.

Methods for the alignment of sequences for comparison are well known inthe art, such methods include GAP, BESTFIT, BLAST, FASTA and TFASTA. GAPuses the algorithm of Needleman and Wunsch ((1970) J Mol Biol 48:443-453) to find the global (i.e. spanning the complete sequences)alignment of two sequences that maximizes the number of matches andminimizes the number of gaps. The BLAST algorithm (Altschul et al.(1990) J Mol Biol 215: 403-10) calculates percent sequence identity andperforms a statistical analysis of the similarity between the twosequences. The software for performing BLAST analysis is publiclyavailable through the National Centre for Biotechnology Information(NCBI). Homologues may readily be identified using, for example, theClustalW multiple sequence alignment algorithm (version 1.83), with thedefault pairwise alignment parameters, and a scoring method inpercentage (See FIG. 1). Global percentages of similarity and identitymay also be determined using one of the methods available in the MatGATsoftware package (Campanella et al., BMC Bioinformatics. 2003 Jul. 10;4:29. MatGAT: an application that generates similarity/identity matricesusing protein or DNA sequences). Minor manual editing may be performedto optimise alignment between conserved motifs, as would be apparent toa person skilled in the art. Furthermore, instead of using full-lengthsequences for the identification of homologues, specific domains mayalso be used. The sequence identity values may be determined over theentire nucleic acid or amino acid sequence or over selected domains orconserved motif(s), using the programs mentioned above using the defaultparameters. For local alignments, the Smith-Waterman algorithm isparticularly useful (Smith T F, Waterman M S (1981) J. Mol. Biol 147(1);195-7).

The proteins of the invention may be altered in various ways includingamino acid substitutions, deletions, truncations, and insertions.Methods for such manipulations are generally known in the art. Forexample, amino acid sequence variants can be prepared by mutations inthe DNA. Methods for mutagenesis and nucleotide sequence alterations arewell known in the art. See, for example, Kunkel (1985) PNAS, 82:488-492;Kunkel et al. (1987) Methods in Enzymol. 154:367-382; U.S. Pat. No.4,873,192; Walker and Gaastra, eds. (1983) Techniques in MolecularBiology (MacMillan Publishing Company, New York) and the referencescited therein. Guidance as to appropriate amino acid substitutions thatdo not affect biological activity of the protein of interest may befound in the model of Dayhoff et al. (1978) Atlas of Protein Sequenceand Structure (Natl. Biomed. Res. Found., Washington, D.C.), hereinincorporated by reference. Conservative substitutions, such asexchanging one amino acid with another having similar properties, may bepreferable.

Alternatively, variant nucleotide sequences can be made by introducingmutations randomly along all or part of a coding sequence, such as bysaturation mutagenesis, and the resultant mutants can be screened toidentify mutants that encode proteins that retain activity. For example,following mutagenesis, the encoded protein can be expressedrecombinantly, and the activity of the protein can be determined usingstandard assay techniques.

The inventors of the present invention have found that by substitutingone or more of the key amino acid residues of the CESA enzyme of SEQ IDNO: 1 or 3, e.g. by employing one of the above described methods tomutate the CESA encoding nucleic acids, the tolerance or resistance toparticular CESA-inhibiting herbicides, collectively named azines, anddescribed in greated detail herein below, could be remarkably increasedPreferred substitutions of mutated CESA are those that increase theherbicide tolerance of the plant, but leave the biological activity ofthe cellulose synthase activity substantially unaffected.

Accordingly, in another object of the present invention refers to a CESApolypeptide, comprising the sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 63, or 64, a variant, derivative, orthologue, paralogue or homologuethereof, the key amino acid residues of which is substituted by anyother amino acid.

It will be understood by the person skilled in the art that amino acidslocated in a close proximity to the positions of amino acids mentionedbelow may also be substituted. Thus, in another embodiment the variantof SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or 64, a variant, derivative,orthologue, paralogue or homologue thereof comprises a mutated CESA,wherein an amino acid ±3, ±2 or ±1 amino acid positions from a key aminoacid is substituted by any other amino acid.

Based on techniques well-known in the art, a highly characteristicsequence pattern can be developed, by means of which further of mutatedCESA candidates with the desired activity may be searched.

Searching for further mutated CESA candidates by applying a suitablesequence pattern would also be encompassed by the present invention. Itwill be understood by a skilled reader that the present sequence patternis not limited by the exact distances between two adjacent amino acidresidues of said pattern. Each of the distances between two neighboursin the above patterns may, for example, vary independently of each otherby up to ±10, ±5, ±3, ±2 or ±1 amino acid positions withoutsubstantially affecting the desired activity.

Furthermore, by applying the method of site directed mutagenesis, inparticular saturation mutagenes (see e.g. Schenk et al., Biospektrum03/2006, pages 277-279) PCR based site-directed mutagenesis (e.g.directed mutagenesis kit, Stratagene, Calif., USA or GeneArt MutagenesisService, ThermoFisher Scientific Inc., Massachusetts, USA) or systematicmutagenesis (GeneArt Systematic Mutagenesis Service, ThermoFisherScientific Inc., Massachusetts, USA), the inventors of the presentinvention have identified and generated specific amino acid subsitutionsand combinations thereof, which—when introduced into a plant bytransforming and expressing the respective mutated CESA encoding nucleicacid—confer increased herbicide resistance or tolerance to a CESAinhibiting herbicide to said plant.

Thus, in preferred embodiment, the variant or derivative of the CESApolypeptide refers to a mutated CESA polypeptide which comprises one ormore of the following motifs:

-   -   i) Motif 1a:

(SEQ ID NO: 78) [V/I] [A/V]G [V/I/F] [S/T] [Y/D/N/A]A [V/I/L] [N/S/G][S/N]G [Y/F/E] [Q/D/G/E/H] [S/A]WG [P/A]L [F/M/L]G [K/R] [L/V] [F/L]F.

-   -   -   Preferably said motif is

(motif 1b; SEQ ID NO: 79) [V/I]AG [V/I]S [Y/D/N]A [V/I] [N/S][S/N]G [Y/F] [Q/D]SWGPL [F/M/L]G [K/R]L [F/L]F.

-   -   -   More preferably said motif is

(motif 1c; SEQ ID NO: 80) VAG [V/I]SYA [V/I]NSGYQSWGPL [F/M]GKL [F/L]F;

-   -   -   Wherein the amino acid at position 5, 16, 17, and/or 20            within said motif is substituted by any other amino acid.

    -   ii) Motif 2a:

(SEQ ID NO: 81) [V/L/I]W [S/A] [V/A/I]LL [A/S]S [I/F/V] [F/L][S/T] [L/V][L/M/V/I]WV [R/K] [I/V] [N/D]PF

-   -   -   Preferably, said motif is

(motif 2b; SEQ ID NO: 82) VW [S/A] [V/A/I]LL [A/S]S [I/F][F/L][S/T][L/V] [L/M]WV [R/K] [I/V] [N/D]PF;

-   -   -   More preferably said motif is

(motif 2c; SEQ ID NO: 83) VW [S/A][V/A/I]LLASIFSL [L/M]WV [R/K]I [N/D]PF

-   -   -   Wherein the amino acid at position 8, and/or 11 within said            motif is substituted by any other amino acid

In a more preferred embodiment, the amino acid corresponding to position5 of motif 1a, 1b, or 1c is:

Arg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp;

And/or

the amino acid corresponding to position 16 of motif 1a, 1b, or 1c isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

And/or

the amino acid corresponding to position 17 of motif 1a, 1b, or 1c isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Gly,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

And/or

the amino acid corresponding to position 20 of motif 1a, 1b, or 1c isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

In another more preferred embodiment, the amino acid corresponding toposition 8 of motif 2a, 2b, or 2c is:

Arg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp;

And/or

the amino acid corresponding to position 11 of motif 2a, 2b, or 2c isArg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

In a particularly preferred embodiment,

the amino acid corresponding to position 5 of motif 1a, 1b, or 1c isPhe,

And/or

the amino acid corresponding to position 16 of motif 1a, 1b, or 1c isAsp,

And/or

the amino acid corresponding to position 17 of motif 1a, 1b, or 1c isLeu,

And/or

the amino acid corresponding to position 20 of motif 1a, 1b, or 1c isArg.

In another more preferred embodiment,

the amino acid corresponding to position 8 of motif 2a, 2b, or 2c isPhe,

And/or

the amino acid corresponding to position 11 of motif 2a, 2b, or 2c isLeu,

In another preferred embodiment, the variant or derivative of the CESApolypeptide refers to a CESA polypeptide comprising SEQ ID NO: 1, aorthologue, paralogue, or homologue thereof, wherein the amino acidsequence differs from the wildtype amino acid sequence of a CESApolypeptide at one or more positions corresponding to the followingpositions of SEQ ID NO:1:

998, 1009, 1010, 1013, 1052, 1055.

Examples of differences at these amino acid positions include, but arenot limited to, one or more of the following:

the amino acid at or corresponding to position 998 is other than serine;

the amino acid at or corresponding to position 1009 is other thanglycine;

the amino acid at or corresponding to position 1010 is other thanproline;

the amino acid at or corresponding to position 1013 is other thanglycine,

the amino acid at or corresponding to position 1052 is other thanserine,

the amino acid at or corresponding to position 1055 is other thanserine,

In some embodiments, the mutated CESA enzyme comprising SEQ ID NO: 1, aorthologue, paralogue, or homologue thereof, comprises one or more ofthe following:

the amino acid corresponding to position 998 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp;

the amino acid corresponding to position 1009 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1010 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Gly,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1013 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1052 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1055 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp.

In a preferred embodiment, the amino acid corresponding to position 1009of SEQ ID NO: 1 is Asp.

In another preferred embodiment, the amino acid corresponding toposition 1010 of SEQ ID NO: 1 is Leu.

In another preferred embodiment, the amino acid corresponding toposition 1013 of SEQ ID NO: 1 is Arg.

In another preferred embodiment, the amino acid corresponding toposition 983 of SEQ ID NO: 3 is Phe.

In another preferred embodiment, the amino acid corresponding toposition 1037 of SEQ ID NO: 3 is Phe.

In another preferred embodiment, the amino acid corresponding toposition 1040 of SEQ ID NO: 3 is Leu.

It will be within the knowledge of the skilled artisan to identifyconserved regions and motifs shared between the homologues, orthologuesand paralogues encoded by SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72, 73,74, 75, 76, or 77, such as those depicted in Table 1. Having identifiedsuch conserved regions that may represent suitable binding motifs, aminoacids corresponding to the amino acids listed below in Table 2, can bechosen to be substituted by any other amino acid, for example byconserved amino acids, preferably by the amino acid substitutionsdescribed SUPRA using SEQ ID NO:1 as reference.

Table 2 provides an overview of positions in the orthologues andhomologues to SEQ ID NO:1, i.e. the corresponding positions in SEQ IDNOs: 1 to 64.

TABLE 2 ID Pos 1 Pos 2 Pos 3 Pos 4 Pos 5 Pos 6 1 S998 G1009 P1010 G1013S1052 S1055 2 S1001 G1012 P1013 G1016 S1055 T1058 3 S983 G994 P995 G998S1037 S1040 4 S967 G978 P979 G982 S1021 S1024 5 S987 G998 P999 G1002S1041 T1044 6 S1002 G1013 P1014 G1017 S1056 T1059 7 S944 G955 P956 G959S998 S1001 8 S901 G912 P913 G916 S955 S958 9 S1005 G1016 P1017 G1020S1059 T1062 10 S985 G996 P997 G1000 S1039 S1042 11 S991 G1002 P1003G1006 S1045 S1048 12 S900 G911 P912 G915 S954 S957 13 S991 G1002 P1003G1006 S1045 S1048 14 S1003 G1014 P1015 G1018 S1057 S1060 15 S974 G985P986 G989 S1028 S1031 16 S995 G1006 P1007 G1010 S1049 S1052 17 S1011G1022 P1023 G1026 S1065 S1068 18 S514 G525 P526 G529 S568 S571 19 S1000G1011 P1012 G1015 S1054 S1057 20 S997 G1008 P1009 G1012 S1051 S1054 21S900 G911 P912 G915 S954 S957 22 — — — — — — 23 S992 G1003 P1004 G1007S1046 S1049 24 S994 G1005 P1006 G1009 S1048 S1051 25 S1006 G1017 P1018G1021 S1060 S1063 26 S951 G962 P963 G966 S1005 S1008 27 S996 G1007 P1008G1011 S1050 T1053 28 S997 G1008 P1009 G1012 S1051 S1054 29 T891 G902A903 G906 S945 S948 30 S891 G902 P903 G906 S945 S948 31 S957 G968 P969G972 S1011 S1014 32 S884 G895 P896 G899 S938 S941 33 T908 G919 A920 G923S962 S965 34 S1002 G1013 P1014 G1017 S1056 S1059 35 S1002 G1013 P1014G1017 S1056 S1059 36 S892 G903 P904 G907 S946 S949 37 S957 G968 P969G972 S1011 S1014 38 S1013 G1024 P1025 G1028 S1067 T1070 39 S905 G916P917 G920 S959 S962 40 S951 G962 P963 G966 S1005 S1008 41 S998 G1009P1010 G1013 S1052 S1055 42 S874 G885 P886 G889 S928 S931 43 S1013 G1024P1025 G1028 S1067 T1070 44 S991 G1002 P1003 G1006 S1045 S1048 45 S992G1003 P1004 G1007 S1046 S1049 46 S1013 G1024 P1025 G1028 S1067 S1070 47S996 G1007 P1008 G1011 S1050 T1053 48 S906 G917 P918 G921 S960 S963 49S991 G1002 P1003 G1006 S1045 S1048 50 S1009 G1020 P1021 G1024 S1063S1066 51 S993 G1004 P1005 G1008 S1047 S1050 52 S1091 S1102 K1103 G1106I1145 S1148 53 S935 S946 K947 G950 I989 S992 54 A778 G790 A791 A794 S834S837 55 S999 G1010 P1011 G1014 S1053 S1056 56 S1009 G1020 P1021 G1024S1063 S1066 57 S1010 G1021 P1022 G1025 S1064 S1067 58 S754 G765 P766G769 S808 S811 59 S883 G894 P895 G898 S937 S940 60 A1033 G1044 K1045G1048 I1087 S1090 61 S973 G984 P985 G988 S1027 S1030 62 S981 G992 P993G996 S1035 S1038 63 S1046 S1057 K1058 G1061 I1100 S1103 64 A1134 S1145K1146 G1149 M1188 S1191

Another object refers to a method of identifying a nucleotide sequenceencoding a mutated CESA which is resistant or tolerant to aCESA-inhibiting herbicide, the method comprising:

-   a) generating a library of mutated CESA-encoding nucleic acids,-   b) screening a population of the resulting mutated CESA-encoding    nucleic acids by expressing each of said nucleic acids in a cell or    plant and treating said cell or plant with a CESA-inhibiting    herbicide,-   c) comparing the CESA-inhibiting herbicide-tolerance levels provided    by said population of mutated CESA encoding nucleic acids with the    CESA-inhibiting herbicide-tolerance level provided by a control    CESA-encoding nucleic acid,-   d) selecting at least one mutated CESA-encoding nucleic acid that    provides a significantly increased level of tolerance to a    CESA-inhibiting herbicide as compared to that provided by the    control CESA-encoding nucleic acid.

In a preferred embodiment, the mutated CESA-encoding nucleic acidselected in step d) provides at least 2-fold as much resistance ortolerance of a cell or plant to a CESA-inhibiting herbicide as comparedto that provided by the control CESA-encoding nucleic acid.

In a further preferred embodiment, the mutated CESA-encoding nucleicacid selected in step d) provides at least 2-fold, at least 5-fold, atleast 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, atleast 500-fold, as much resistance or tolerance of a cell or plant to aCESA-inhibiting herbicide as compared to that provided by the controlCESA-encoding nucleic acid.

The resistance or tolerance can be determined by generating a transgenicplant or host cell, preferably a plant cell, comprising a nucleic acidsequence of the library of step a) and comparing said transgenic plantwith a control plant or host cell, preferably a plant cell.

Another object refers to a method of identifying a plant or algaecontaining a nucleic acid comprising a nucleotide sequence encoding awildtype or mutated CESA which is resistant or tolerant to aCESA-inhibiting herbicide, the method comprising:

-   a) identifying an effective amount of a CESA-inhibiting herbicide in    a culture of plant cells or green algae that leads to death of said    cells.-   b) treating said plant cells or green algae with a mutagenizing    agent,-   c) contacting said mutagenized cells population with an effective    amount of CESA-inhibiting herbicide, identified in a),-   d) selecting at least one cell surviving these test conditions,-   e) PCR-amplification and sequencing of CESA genes from cells    selected in d) and comparing such sequences to wild-type CESA gene    sequences, respectively.

In a preferred embodiment, said mutagenizing agent isethylmethanesulfonate (EMS).

Many methods well known to the skilled artisan are available forobtaining suitable candidate nucleic acids for identifying a nucleotidesequence encoding a wildtype or mutated CESA from a variety of differentpotential source organisms including microbes, plants, fungi, algae,mixed cultures etc. as well as environmental sources of DNA such assoil. These methods include inter alia the preparation of cDNA orgenomic DNA libraries, the use of suitably degenerate oligonucleotideprimers, the use of probes based upon known sequences or complementationassays (for example, for growth upon tyrosine) as well as the use ofmutagenesis and shuffling in order to provide recombined or shuffledwildtype or mutated CESA-encoding sequences.

Nucleic acids comprising candidate and control CESA encoding sequencescan be expressed in yeast, in a bacterial host strain, in an alga or ina higher plant such as tobacco or Arabidopsis and the relative levels ofinherent tolerance of the CESA encoding sequences screened according toa visible indicator phenotype of the transformed strain or plant in thepresence of different concentrations of the selected CESA-inhibitingherbicide. Dose responses and relative shifts in dose responsesassociated with these indicator phenotypes (formation of necrosis,growth inhibition, herbicidal effect etc) are conveniently expressed interms, for example, of GR50 (concentration for 50% reduction of growth)or MIC (minimum inhibitory concentration) values where increases invalues correspond to increases in inherent tolerance of the expressedCESA. For example, in a relatively rapid assay system based upontransformation of Arabidopsis as described in the Example section(Example 7), each wildtype or mutated CESA encoding sequence may beexpressed, for example, as a DNA sequence under expression control of asuitable promoter and T1 plants can be selected for differentialtolerance to selected CESA-inhibiting herbicides, measured by growth.

In another embodiment, candidate nucleic acids are transformed intoplant material to generate a transgenic plant, regenerated intomorphologically normal fertile plants which are then measured fordifferential tolerance to selected CESA-inhibiting herbicides asdescribed in the Example section hereinafter. Many suitable methods fortransformation using suitable selection markers such as kanamycin,binary vectors such as from Agrobacterium and plant regeneration as, forexample, from tobacco leaf discs are well known in the art. Optionally,a control population of plants is likewise transformed with a nucleicacid expressing the control CESA. Alternatively, an untransformed dicotplant such as Arabidopsis or Tobacco can be used as a control sincethis, in any case, expresses its own endogenous CESA. The average, anddistribution, of herbicide tolerance levels of a range of primary planttransformation events or their progeny to CESA-inhibiting herbicidesdescribed supra are evaluated in the normal manner based upon plantdamage, meristematic bleaching symptoms etc. at a range of differentconcentrations of herbicides. These data can be expressed in terms of,for example, GR50 values derived from dose/response curves having “dose”plotted on the x-axis and “percentage kill”, “herbicidal effect”,“numbers of emerging green plants” etc. plotted on the y-axis whereincreased GR50 values correspond to increased levels of inherenttolerance of the expressed CESA. Herbicides can suitably be appliedpre-emergence or post-emergence.

Another object of the present invention refers to an isolated and orrecombinantly produced and/or synthetic nucleic acid encoding a mutatedCESA as disclosed SUPRA, wherein the nucleic acid comprises thenucleotide sequence of SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72, 73,74, 75, 76, or 77, or a variant or derivative thereof.

In one embodiment, the nucleic acid is identifiable by a method asdefined above.

For the purposes of the invention “recombinant” means with regard forexample to a nucleic acid sequence, an expression cassette (=geneconstruct, nucleic acid construct) or a vector containing the nucleicacid sequence according to the invention or an organism transformed bysaid nucleic acid sequences, expression cassette or vector according tothe invention all those constructions produced by genetic engineeringmethods in which either

(a) the nucleic acid sequence comprising the sequence of SEQ ID NO: 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, or 77, or a homolog thereof,or its derivatives or parts thereof; or

(b) a genetic control sequence functionally linked to the nucleic acidsequence described under (a), for example a 3′- and/or 5′-geneticcontrol sequence such as a promoter or terminator, or

(c) (a) and (b);

are not found in their natural, genetic environment or have beenmodified by genetic engineering methods, wherein the modification may byway of example be a substitution, addition, deletion, inversion orinsertion of one or more nucleotide residues.

“Natural genetic environment” means the natural genomic or chromosomallocus in the organism of origin or inside the host organism or presencein a genomic library. In the case of a genomic library the naturalgenetic environment of the nucleic acid sequence is preferably retainedat least in part. The environment borders the nucleic acid sequence atleast on one side and has a sequence length of at least 50 bp,preferably at least 500 bp, particularly preferably at least 1,000 bp,most particularly preferably at least 5,000 bp. A naturally occurringexpression cassette for example the naturally occurring combination ofthe natural promoter of the nucleic acid sequence according to theinvention with the corresponding gene—turns into a transgenic expressioncassette when the latter is modified by unnatural, synthetic(“artificial”) methods such as by way of example a mutagenation.Appropriate methods are described by way of example in U.S. Pat. No.5,565,350 or WO 00/15815

In a preferred embodiment, the encoded mutated CESA is a variant of SEQID NO: 1, which includes one or more of the following:

the amino acid corresponding to position 998 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp;

the amino acid corresponding to position 1009 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1010 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Gly,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1013 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Ser,Thr,Asn,Gln,Cys,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1052 of SEQ ID NO:1 isArg,His,Lys,Asp,Glu,Thr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp,

the amino acid corresponding to position 1055 of SEQ ID NO:1 isArg,His,Lys,Asp,GluThr,Asn,Gln,Cys,Gly,Pro,Ala,Val,Leu,Ile,Met,Phe,Tyr,or Trp.

In a preferred embodiment, the amino acid corresponding to position 1009of SEQ ID NO: 1 is Asp.

In another preferred embodiment, the amino acid corresponding toposition 1010 of SEQ ID NO: 1 is Leu.

In another preferred embodiment, the amino acid corresponding toposition 1013 of SEQ ID NO: 1 is Arg.

In another preferred embodiment, the amino acid corresponding toposition 983 of SEQ ID NO: 3 is Phe.

In another preferred embodiment, the amino acid corresponding toposition 1037 of SEQ ID NO: 3 is Phe.

In another preferred embodiment, the amino acid corresponding toposition 1040 of SEQ ID NO: 3 is Leu.

In other aspects, the present invention encompasses a progeny or adescendant of a CESA-inhibiting herbicides-tolerant plant of the presentinvention as well as seeds derived from the CESA-inhibitingherbicides-tolerant plants of the invention and cells derived from theCESA-inhibiting herbicides-tolerant plants of the invention.

In some embodiments, the present invention provides a progeny ordescendant plant derived from a plant comprising in at least some of itscells a polynucleotide operably linked to a promoter operable in plantcells, the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, wherein the progeny ordescendant plant comprises in at least some of its cells the recombinantpolynucleotide operably linked to the promoter, the expression of thewildtype or mutated CESA polypeptide conferring to the progeny ordescendant plant tolerance to the CESA-inhibiting herbicides.

In one embodiment, seeds of the present invention preferably comprisethe CESA-inhibiting herbicides-tolerance characteristics of theCESA-inhibiting herbicides-tolerant plant. In other embodiments, a seedis capable of germination into a plant comprising in at least some ofits cells a polynucleotide operably linked to a promoter operable inplant cells, the promoter capable of expressing a wildtype or mutatedCESA polypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the progeny ordescendant plant tolerance to the CESA-inhibiting herbicides.

In some embodiments, plant cells of the present invention are capable ofregenerating a plant or plant part. In other embodiments, plant cellsare not capable of regenerating a plant or plant part. Examples of cellsnot capable of regenerating a plant include, but are not limited to,endosperm, seed coat (testa & pericarp), and root cap.

In another embodiment, the present invention provides a plant cell of orcapable of regenerating a plant comprising in at least some of its cellsa polynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto the CESA-inhibiting herbicides, wherein the plant cell comprises therecombinant polynucleotide operably linked to a promoter.

In other embodiments, the present invention provides a plant cellcomprising a polynucleotide operably linked to a promoter operable inplant cells, the promoter capable of expressing a wildtype or mutatedCESA polypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the cell tolerance tothe CESA-inhibiting herbicides.

In another embodiment, the invention refers to a plant cell transformedby a nucleic acid encoding a wildtype or mutated CESA polypeptideaccording to the present invention or to a plant cell which has beenmutated to obtain a plant expressing a nucleic acid encoding a wildtypeor mutated CESA polypeptide according to the present invention, whereinexpression of the nucleic acid in the plant cell results in increasedresistance or tolerance to a CESA-inhibiting herbicide as compared to awild type variety of the plant cell. Preferably, the wildtype or mutatedCESA polypeptide encoding nucleic acid comprises a polynucleotidesequence selected from the group consisting of: a) a polynucleotide asshown in SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, or77, or a variant or derivative thereof; b) a polynucleotide encoding apolypeptide as shown in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, or 64,or a variant or derivative thereof; c) a polynucleotide comprising atleast 60 consecutive nucleotides of any of a) or b); and d) apolynucleotide complementary to the polynucleotide of any of a) throughc).

In some aspects, the present invention provides a plant product preparedfrom the CESA-inhibiting herbicides-tolerant plants hereof. In someembodiments, examples of plant products include, without limitation,grain, oil, and meal. In one embodiment, a plant product is plant grain(e.g., grain suitable for use as feed or for processing), plant oil(e.g., oil suitable for use as food or biodiesel), or plant meal (e.g.,meal suitable for use as feed).

In one embodiment, a plant product prepared from a plant or plant partis provided, wherein the plant or plant part comprises in at least someof its cells a polynucleotide operably linked to a promoter operable inplant cells, the promoter capable of expressing a wildtype or mutatedCESA polypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the a plant or plantpart tolerance to the CESA-inhibiting herbicides.

In another embodiment, the invention refers to a method of producing atransgenic plant cell with an increased resistance to a CESA-inhibitingherbicide as compared to a wild type variety of the plant cellcomprising, transforming the plant cell with an expression cassettecomprising a polynucleotide operably linked to a promoter operable inplant cells, the promoter capable of expressing a wildtype or mutatedCESA polypeptide encoded by the polynucleotide.

In another embodiment, the invention refers to a method of producing atransgenic plant comprising, (a) transforming a plant cell with anexpression cassette comprising a a polynucleotide operably linked to apromoter operable in plant cells, the promoter capable of expressing awildtype or mutated CESA polypeptide encoded by the polynucleotide, and(b) generating a plant with an increased resistance to CESA-inhibitingherbicide from the plant cell.

In some aspects, the present invention provides a method for producing aCESA-inhibiting herbicides-tolerant plant. In one embodiment, the methodcomprises: regenerating a plant from a plant cell transformed with apolynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto the CESA-inhibiting herbicides.

The term “expression/expressing” or “gene expression” means thetranscription of a specific gene or specific genes or specific geneticconstruct. The term “expression” or “gene expression” in particularmeans the transcription of a gene or genes or genetic construct intostructural RNA (rRNA, tRNA) or mRNA with or without subsequenttranslation of the latter into a protein. The process includestranscription of DNA and processing of the resulting mRNA product.

To obtain the desired effect, i.e. plants that are tolerant or resistantto the CESA-inhibiting herbicide derivative herbicide of the presentinvention, it will be understood that the at least one nucleic acid is“over-expressed” by methods and means known to the person skilled in theart.

The term “increased expression” or “overexpression” as used herein meansany form of expression that is additional to the original wild-typeexpression level. Methods for increasing expression of genes or geneproducts are well documented in the art and include, for example,overexpression driven by appropriate promoters, the use of transcriptionenhancers or translation enhancers. Isolated nucleic acids which serveas promoter or enhancer elements may be introduced in an appropriateposition (typically upstream) of a non-heterologous form of apolynucleotide so as to upregulate expression of a nucleic acid encodingthe polypeptide of interest. For example, endogenous promoters may bealtered in vivo by mutation, deletion, and/or substitution (see, Kmiec,U.S. Pat. No. 5,565,350; Zarling et al., WO9322443), or isolatedpromoters may be introduced into a plant cell in the proper orientationand distance from a gene of the present invention so as to control theexpression of the gene. If polypeptide expression is desired, it isgenerally desirable to include a polyadenylation region at the 3′-end ofa polynucleotide coding region. The polyadenylation region can bederived from the natural gene, from a variety of other plant genes, orfrom T-DNA. The 3′ end sequence to be added may be derived from, forexample, the nopaline synthase or octopine synthase genes, oralternatively from another plant gene, or less preferably from any othereukaryotic gene. An intron sequence may also be added to the 5′untranslated region (UTR) or the coding sequence of the partial codingsequence to increase the amount of the mature message that accumulatesin the cytosol. Inclusion of a spliceable intron in the transcriptionunit in both plant and animal expression constructs has been shown toincrease gene expression at both the mRNA and protein levels up to1000-fold (Buchman and Berg (1988) Mol. Cell biol. 8: 4395-4405; Calliset al. (1987) Genes Dev 1:1183-1200). Such intron enhancement of geneexpression is typically greatest when placed near the 5′ end of thetranscription unit. Use of the maize introns Adh1-S intron 1, 2, and 6,the Bronze-1 intron are known in the art. For general information see:The Maize Handbook, Chapter 116, Freeling and Walbot, Eds., Springer,N.Y. (1994).

Where appropriate, nucleic acid sequences may be optimized for increasedexpression in a transformed plant. For example, coding sequences thatcomprise plant-preferred codons for improved expression in a plant canbe provided. See, for example, Campbell and Gowri (1990) Plant Physiol.,92: 1-11 for a discussion of host-preferred codon usage. Methods alsoare known in the art for preparing plant-preferred genes. See, forexample, U.S. Pat. Nos. 5,380,831, and 5,436,391, and Murray et al.(1989) Nucleic Acids Res. 17:477-498, herein incorporated by reference.

Consequently, wildtype or mutated CESA nucleic acids of the inventionare provided in expression cassettes for expression in the plant ofinterest. The cassette will include regulatory sequences operably linkedto a wildtype or mutated CESA nucleic acid sequence of the invention.The term “regulatory element” as used herein refers to a polynucleotidethat is capable of regulating the transcription of an operably linkedpolynucleotide. It includes, but not limited to, promoters, enhancers,introns, 5′ UTRs, and 3′ UTRs. By “operably linked” is intended afunctional linkage between a promoter and a second sequence, wherein thepromoter sequence initiates and mediates transcription of the DNAsequence corresponding to the second sequence. Generally, operablylinked means that the nucleic acid sequences being linked are contiguousand, where necessary to join two protein coding regions, contiguous andin the same reading frame. The cassette may additionally contain atleast one additional gene to be cotransformed into the organism.Alternatively, the additional gene(s) can be provided on multipleexpression cassettes.

Such an expression cassette is provided with a plurality of restrictionsites for insertion of the wildtype or mutated CESA nucleic acidsequence to be under the transcriptional regulation of the regulatoryregions. The expression cassette may additionally contain selectablemarker genes. The expression cassette of the present invention willinclude in the 5′-3′ direction of transcription, a transcriptional andtranslational initiation region (i.e., a promoter), a wildtype ormutated CESA encoding nucleic acid sequence of the invention, and atranscriptional and translational termination region (i.e., terminationregion) functional in plants. The promoter may be native or analogous,or foreign or heterologous, to the plant host and/or to the wildtype ormutated CESA nucleic acid sequence of the invention. Additionally, thepromoter may be the natural sequence or alternatively a syntheticsequence. Where the promoter is “foreign” or “heterologous” to the planthost, it is intended that the promoter is not found in the native plantinto which the promoter is introduced. Where the promoter is “foreign”or “heterologous” to the wildtype or mutated CESA nucleic acid sequenceof the invention, it is intended that the promoter is not the native ornaturally occurring promoter for the operably linked wildtype or mutatedCESA nucleic acid sequence of the invention. As used herein, a chimericgene comprises a coding sequence operably linked to a transcriptioninitiation region that is heterologous to the coding sequence. While itmay be preferable to express the wildtype or mutated CESA nucleic acidsof the invention using heterologous promoters, the native promotersequences may be used. Such constructs would change expression levels ofthe wildtype or mutated CESA protein in the plant or plant cell. Thus,the phenotype of the plant or plant cell is altered.

The termination region may be native with the transcriptional initiationregion, may be native with the operably linked wildtype or mutated CESAsequence of interest, may be native with the plant host, or may bederived from another source (i.e., foreign or heterologous to thepromoter, the wildtype or mutated CESA nucleic acid sequence ofinterest, the plant host, or any combination thereof). Convenienttermination regions are available from the Ti-plasmid of A. tumefaciens,such as the octopine synthase and nopaline synthase termination regions.See also Guerineau et al. (1991) Mol. Gen. Genet. 262: 141-144;Proudfoot (1991) Cell 64:671-674; Sanfacon et al. (1991) Genes Dev. 5:141-149; Mogen et al. (1990) Plant Cell 2: 1261-1272; Munroe et al.(1990) Gene 91: 151-158; Ballast al. (1989) Nucleic Acids Res.17:7891-7903; and Joshi et al. (1987) Nucleic Acid Res. 15:9627-9639.Where appropriate, the gene(s) may be optimized for increased expressionin the transformed plant. That is, the genes can be synthesized usingplant-preferred codons for improved expression. See, for example,Campbell and Gowri (1990) Plant Physiol. 92: 1-11 for a discussion ofhost-preferred codon usage. Methods are available in the art forsynthesizing plant-preferred genes. See, for example, U.S. Pat. Nos.5,380,831, and 5,436,391, and Murray et al. (1989) Nucleic Acids Res.17:477-498, herein incorporated by reference.

While the polynucleotides of the invention may find use as selectablemarker genes for plant transformation, the expression cassettes of theinvention can include another selectable marker gene for the selectionof transformed cells. Selectable marker genes, including those of thepresent invention, are utilized for the selection of transformed cellsor tissues. Marker genes include, but are not limited to, genes encodingantibiotic resistance, such as those encoding neomycinphosphotransferase II (NEO) and hygromycin phosphotransferase (HPT), aswell as genes conferring resistance to herbicidal compounds, such asglufosinate ammonium, bromoxynil, imidazolinones, and2,4-dichlorophenoxyacetate (2,4-D). See generally, Yarranton (1992)Curr. Opin. Biotech. 3:506-511; Christophers on et al (1992) Proc. Natl.Acad. ScL USA 89:6314-6318; Yao et al. (1992) Cell 71:63-72; Reznikoff(1992) Mol Microbiol 6:2419-2422; Barkley et al (1980) in The Operon,pp. 177-220; Hu et al (1987) Cell 48:555-566; Brown et al (1987) Cell49:603-612; Figge et al (1988) Cell 52:713-722; Deuschle et al (1989)Proc. Natl Acad. AcL USA 86:5400-5404; Fuerst et al (1989) Proc. NatlAcad. ScL USA 86:2549-2553; Deuschle et al (1990) Science 248:480-483;Gossen (1993) Ph.D. Thesis, University of Heidelberg; Reines et al(1993) Proc. Natl Acad. ScL USA 90: 1917-1921; Labow et al (1990) MolCell Biol 10:3343-3356; Zambretti et al (1992) Proc. Natl Acad. ScL USA89:3952-3956; Bairn et al (1991) Proc. Natl Acad. ScL USA 88:5072-5076;Wyborski et al (1991) Nucleic Acids Res. 19:4647-4653; Hillenand-Wissman(1989) Topics Mol Struc. Biol 10: 143-162; Degenkolb et al (1991)Antimicrob. Agents Chemother. 35: 1591-1595; Kleinschnidt et al (1988)Biochemistry 27: 1094-1104; Bonin (1993) Ph.D. Thesis, University ofHeidelberg; Gossen et al (1992) Proc. Natl Acad. ScL USA 89:5547-5551;Oliva et al (1992) Antimicrob. Agents Chemother. 36:913-919; Hlavka etal (1985) Handbook of Experimental Pharmacology, Vol. 78(Springer-Verlag, Berlin); Gill et al (1988) Nature 334:721-724. Suchdisclosures are herein incorporated by reference. The above list ofselectable marker genes is not meant to be limiting. Any selectablemarker gene can be used in the present invention.

Further, additional sequence modifications are known to enhance geneexpression in a cellular host. These include elimination of sequencesencoding spurious polyadenylation signals, exon-intron splice sitesignals, transposon-like repeats, and other such well-characterizedsequences that may be deleterious to gene expression. The G-C content ofthe sequence may be adjusted to levels average for a given cellularhost, as calculated by reference to known genes expressed in the hostcell. Also, if desired, sequences can be readily modified to avoidpredicted hairpin secondary mRNA structures. Nucleotide sequences forenhancing gene expression can also be used in the plant expressionvectors. These include, for example, introns of the maize Adh geneAdh1-S intron 1, 2, and 6 (Callis et al. Genes and Development 1:1183-1200, 1987), and leader sequences, (W-sequence) from the TobaccoMosaic virus (TMV), Maize Chlorotic Mottle Virus and Alfalfa MosaicVirus (Gallie et al. Nucleic Acid Res. 15:8693-8711, 1987 and Skuzeskiet al. Plant Mol. Biol. 15:65-79, 1990). The first intron from theshrunken-1 locus of maize has been shown to increase expression of genesin chimeric gene constructs. U.S. Pat. Nos. 5,424,412 and 5,593,874disclose the use of specific introns in gene expression constructs, andGallie et al. (Plant Physiol. 106:929-939, 1994) also have shown thatintrons are useful for regulating gene expression on a tissue specificbasis. To further enhance or to optimize gene expression, the plantexpression vectors of the invention also may contain DNA sequencescontaining matrix attachment regions (MARs). Plant cells transformedwith such modified expression systems, then, may exhibit overexpressionor constitutive expression of a nucleotide sequence of the invention.

The invention further provides an isolated recombinant expression vectorcomprising the expression cassette containing a wildtype or mutated CESAnucleic acid nucleic acid as described above, wherein expression of thevector in a host cell results in increased tolerance to aCESA-inhibiting herbicide as compared to a wild type variety of the hostcell. As used herein, the term “vector” refers to a nucleic acidmolecule capable of transporting another nucleic acid to which it hasbeen linked. One type of vector is a “plasmid,” which refers to acircular double stranded DNA loop into which additional DNA segments canbe ligated. Another type of vector is a viral vector, wherein additionalDNA segments can be ligated into the viral genome. Certain vectors arecapable of autonomous replication in a host cell into which they areintroduced (e.g., bacterial vectors having a bacterial origin ofreplication and episomal mammalian vectors). Other vectors (e.g.,non-episomal mammalian vectors) are integrated into the genome of a hostcell upon introduction into the host cell, and thereby are replicatedalong with the host genome. Moreover, certain vectors are capable ofdirecting the expression of genes to which they are operatively linked.Such vectors are referred to herein as “expression vectors.” In general,expression vectors of utility in recombinant DNA techniques are often inthe form of plasmids. In the present specification, “plasmid” and“vector” can be used interchangeably as the plasmid is the most commonlyused form of vector. However, the invention is intended to include suchother forms of expression vectors, such as viral vectors (e.g.,replication defective retroviruses, adenoviruses, and adeno-associatedviruses), which serve equivalent functions.

The recombinant expression vectors of the invention comprise a nucleicacid of the invention in a form suitable for expression of the nucleicacid in a host cell, which means that the recombinant expression vectorsinclude one or more regulatory sequences, selected on the basis of thehost cells to be used for expression, which is operably linked to thenucleic acid sequence to be expressed. Regulatory sequences includethose that direct constitutive expression of a nucleotide sequence inmany types of host cells and those that direct expression of thenucleotide sequence only in certain host cells or under certainconditions. It will be appreciated by those skilled in the art that thedesign of the expression vector can depend on such factors as the choiceof the host cell to be transformed, the level of expression ofpolypeptide desired, etc. The expression vectors of the invention can beintroduced into host cells to thereby produce polypeptides or peptides,including fusion polypeptides or peptides, encoded by nucleic acids asdescribed herein (e.g., wildtype or mutated CESA polypeptides, fusionpolypeptides, etc.)

Expression vectors may additionally contain 5′ leader sequences in theexpression construct. Such leader sequences can act to enhancetranslation. Translation leaders are known in the art and include:picornavirus leaders, for example, EMCV leader (Encephalomyo carditis 5′noncoding region) (Elroy-Stein et al. (1989) PNAS, 86:6126-6130);potyvirus leaders, for example, TEV leader (Tobacco Etch Virus) (Gallieet al. (1995) Gene 165(2):233-238), MDMV leader (Maize Dwarf MosaicVirus) (Virology 154:9-20), and human immunoglobulin heavy-chain bindingprotein (BiP) (Macejak et al. (1991) Nature 353:90-94); untranslatedleader from the coat protein mRNA of alfalfa mosaic virus (AMV RNA 4)(Jobling et al. (1987) Nature 325:622-625); tobacco mosaic virus leader(TMV) (Gallie et al. (1989) in Molecular Biology of RNA, ed. Cech (Liss,New York), pp. 237-256); and maize chlorotic mottle virus leader (MCMV)(Lommel et al. (1991) Virology 81:382-385). See also, Della-Cioppa etal. (1987) Plant Physiol. 84:965-968.

Other methods known to enhance translation also can be utilized, forexample, introns, and the like. In preparing an expression vector, thevarious nucleic acid fragments may be manipulated, so as to provide forthe nucleic acid sequences in the proper orientation and, asappropriate, in the proper reading frame. Toward this end, adapters orlinkers may be employed to join the nucleic acid fragments or othermanipulations may be involved to provide for convenient restrictionsites, removal of superfluous nucleic acid, removal of restrictionsites, or the like. For this purpose, in vitro mutagenesis, primerrepair, restriction, annealing, resubstitutions, e.g., transitions andtransversions, may be involved.

A number of promoters can be used in the practice of the invention. Thepromoters can be selected based on the desired outcome. The nucleicacids can be combined with constitutive, tissue-preferred, or otherpromoters for expression in plants.

Constitutive promoters include, for example, the core promoter of theRsyn7 promoter and other constitutive promoters disclosed in WO 99/43838and U.S. Pat. No. 6,072,050; the core CaMV 35S promoter (Odell et al.(1985) Nature 313:810-812); rice actin (McElroy et al. (1990) Plant Cell2: 163-171); ubiquitin (Christensen et al. (1989) Plant Mol. Biol.12:619-632 and Christensen et al. (1992) Plant Mol. Biol. 18:675-689);pEMU (Last et al. (1991) Theor. Appl. Genet. 81:581-588); MAS (Velten etal. (1984) EMBO J. 3:2723-2730); ALS promoter (U.S. Pat. No. 5,659,026),and the like. Other constitutive promoters include, for example, U.S.Pat. Nos. 5,608,149; 5,608,144; 5,604,121; 5,569,597; 5,466,785;5,399,680; 5,268,463; 5,608,142; and 6,177,611.

Tissue-preferred promoters can be utilized to target enhanced expressionwithin a particular plant tissue. Such tissue-preferred promotersinclude, but are not limited to, leaf-preferred promoters,root-preferred promoters, seed-preferred promoters, and stem-preferredpromoters. Some examples of tissue-preferred promoters are described by,e.g., Yamamoto et al. (1997) Plant J. 12(2):255-265; Kawamata et al.(1997) Plant Cell Physiol. 38(7):792-803; Hansen et al. (1997) Mol. GenGenet. 254(3):337-343; Russell et al. (1997) Transgenic Res. 6(2):157-168; Rinehart et al. (1996) Plant Physiol. 1 12(3): 1331-1341; VanCamp et al. (1996) Plant Physiol. 112(2):525-535; Canevascini et al.(1996) Plant Physiol. 1 12(2):513-524; Yamamoto et al. (1994) Plant CellPhysiol. 35(5):773-778; Lam (1994) Results Probl. Cell Differ.20:181-196; Orozco of al. (1993) Plant Mol Biol. 23(6): 1 129-1138;Matsuoka et al. (1993) Voc Natl. Acad. ScL USA 90(20):9586-9590; andGuevara-Garcia et al. (1993) Plant J 4(3):495-505. Promoters can bemodified, if necessary, for weak expression.

In some embodiments, the nucleic acids of interest can be targeted tothe chloroplast for expression. In this manner, where the nucleic acidof interest is not directly inserted into the chloroplast, theexpression vector will additionally contain a chloroplast-targetingsequence comprising a nucleotide sequence that encodes a chloroplasttransit peptide to direct the gene product of interest to thechloroplasts. Such transit peptides are known in the art. With respectto chloroplast-targeting sequences, “operably linked” means that thenucleic acid sequence encoding a transit peptide (i.e., thechloroplast-targeting sequence) is linked to the desired coding sequenceof the invention such that the two sequences are contiguous and in thesame reading frame. See, for example, Von Heijne et al. (1991) PlantMol. Biol. Rep. 9: 104-126; Clark et al. (1989) J Biol. Chem.264:17544-17550; Della-Cioppa et al. (1987) Plant Physiol. 84:965-968;Romer et al. (1993) Biochem. Biophys. Res. Commun. 196: 1414-1421; andShah et al. (1986) Science 233:478-481. For example, a chloroplasttransit peptide known in the art can be fused to the amino acid sequenceof a CESA polypeptide of the invention by operably linking achloroplast-targeting sequence to the 5′-end of a nucleotide sequenceencoding the CESA polypeptide.

Chloroplast targeting sequences are known in the art and include thechloroplast small subunit of ribulose-1,5-bisphosphate carboxylase(Rubisco) (de Castro Silva Filho et al. (1996) Plant Mol. Biol.30:769-780; Schnell et al. (1991) J Biol. Chem. 266(5):3335-3342); EPSPS(Archer et al. (1990) J Bioenerg. Biomemb. 22(6):789-810); tryptophansynthase (Zhao et al. (1995) J Biol. Chem. 270(11):6081-6087);plastocyanin (Lawrence et al. (1997) J Biol. Chem. 272(33):20357-20363);chorismate synthase (Schmidt et al. (1993) J Biol. Chem.268(36):27447-27457); and the light harvesting chlorophyll a/b bindingprotein (LHBP) (Lamppa et al. (1988) J Biol. Chem. 263: 14996-14999).See also Von Heijne et al. (1991) Plant Mol. Biol. Rep. 9: 104-126;Clark et al. (1989) J Biol. Chem. 264: 17544-17550; Della-Cioppa et al.(1987) Plant Physiol. 84:965-968; Romer et al. (1993) Biochem Biophys.Res. Commun. 196: 1414-1421; and Shah et al. (1986) Science 233:478-481.

Methods for transformation of chloroplasts are known in the art. See,for example, Svab et al. (1990) Proc. Natl. Acad. ScL USA 87:8526-8530;Svab and Maliga (1993) Proc. Natl. Acad. Sci. USA 90:913-917; Svab andMaliga (1993) EMBO J. 12:601-606. The method relies on particle gundelivery of DNA containing a selectable marker and targeting of the DNAto the plastid genome through homologous recombination. Additionally,plastid transformation can be accomplished by transactivation of asilent plastid-borne transgene by tissue-preferred expression of anuclear-encoded and plastid-directed RNA polymerase. Such a system hasbeen reported in McBride et al. (1994) Proc. Natl. Acad. Sci. USA91:7301-7305.

The nucleic acids of interest to be targeted to the chloroplast may beoptimized for expression in the chloroplast to account for differencesin codon usage between the plant nucleus and this organelle. In thismanner, the nucleic acids of interest may be synthesized usingchloroplast-preferred codons. See, for example, U.S. Pat. No. 5,380,831,herein incorporated by reference.

Numerous plant transformation vectors and methods for transformingplants are available. See, for example, An, G. et al. (1986) PlantPysioL, 81:301-305; Fry, J., et al. (1987) Plant Cell Rep. 6:321-325;Block, M. (1988) Theor. Appl. Genet.16: 161-1 1 A; Hinchee, et al.(1990) Stadler. Genet. Symp.2032\2.203-2\2; Cousins, et al. (1991) Aust.J. Plant Physiol. 18:481-494; Chee, P. P. and Slightom, J. L. (1992)Gene.I I 8:255-260; Christou, et al. (1992) Trends. Biotechnol.10:239-246; Halluin, et al. (1992) Bio/Technol. 10:309-314; Dhir, et al.(1992) Plant Physiol. 99:81-88; Casas et al. (1993) Proc. Nat. Acad Sd.USA 90: 1 1212-1 1216; Christou, P. (1993) In Vitro Cell. Dev.Biol.-Plant; 29P.119-124; Davies, et al. (1993) Plant Cell Rep. 12:180-183; Dong, J. A. and Mchughen, A. (1993) Plant ScL 91: 139-148;Franklin, C. I. and Trieu, T. N. (1993) Plant. Physiol. 102: 167;Golovkin, et al. (1993) Plant ScL 90:41-52; Guo Chin ScL Bull.38:2072-2078; Asano, et al. (1994) Plant Cell Rep. 13; Ayeres N. M. andPark, W. D. (1994) Crit. Rev. Plant. Sci. 13:219-239; Barcelo, et al.(1994) Plant. J. 5:583-592; Becker, et al. (1994) Plant. J. 5:299-307;Borkowska et al. (1994) Acta. Physiol Plant. 16:225-230; Christou, P.(1994) Agro. Food. Ind. Hi Tech. 5: 17-27; Eapen et al. (1994) PlantCell Rep. 13:582-586; Hartman, et al. (1994) Bio-Technology 12: 919923;Ritala, et al. (1994) Plant. Mol. Biol. 24:317-325; and Wan, Y. C. andLemaux, P. G. (1994) Plant Physiol. 104:3748.

In some embodiments, the methods of the invention involve introducing apolynucleotide construct into a plant. By “introducing” is intendedpresenting to the plant the polynucleotide construct in such a mannerthat the construct gains access to the interior of a cell of the plant.The methods of the invention do not depend on a particular method forintroducing a polynucleotide construct to a plant, only that thepolynucleotide construct gains access to the interior of at least onecell of the plant. Methods for introducing polynucleotide constructsinto plants are known in the art including, but not limited to, stabletransformation methods, transient transformation methods, andvirus-mediated methods. The term “introduction” or “transformation” asreferred to herein further means the transfer of an exogenouspolynucleotide into a host cell, irrespective of the method used fortransfer. Plant tissue capable of subsequent clonal propagation, whetherby organogenesis or embryogenesis, may be transformed with a geneticconstruct of the present invention and a whole plant regenerated therefrom. The particular tissue chosen will vary depending on the clonalpropagation systems available for, and best suited to, the particularspecies being transformed. Exemplary tissue targets include leaf disks,pollen, embryos, cotyledons, hypocotyls, megagametophytes, callustissue, existing meristematic tissue (e.g., apical meristem, axillarybuds, and root meristems), and induced meristem tissue (e.g., cotyledonmeristem and hypocotyl meristem). The polynucleotide may be transientlyor stably introduced into a host cell and may be maintainednon-integrated, for example, as a plasmid. Alternatively, it may beintegrated into the host genome. The resulting transformed plant cellmay then be used to regenerate a transformed plant in a manner known topersons skilled in the art.

By “stable transformation” is intended that the polynucleotide constructintroduced into a plant integrates into the genome of the plant and iscapable of being inherited by descendent thereof. By “transienttransformation” is intended that a polynucleotide construct introducedinto a plant does not integrate into the genome of the plant.

For the transformation of plants and plant cells, the nucleotidesequences of the invention are inserted using standard techniques intoany vector known in the art that is suitable for expression of thenucleotide sequences in a plant or plant cell. The selection of thevector depends on the preferred transformation technique and the targetplant species to be transformed. In an embodiment of the invention, theencoding nucleotide sequence is operably linked to a plant promoter,e.g. a promoter known in the art for high-level expression in a plantcell, and this construct is then introduced into a plant cell that issusceptible to CESA-inhibiting herbicides; and a transformed plant isregenerated. In some embodiments, the transformed plant is tolerant toexposure to a level of CESA-inhibiting herbicides that would kill orsignificantly injure a plant regenerated from an untransformed cell.This method can be applied to any plant species or crops.

Methodologies for constructing plant expression vectors and introducingforeign nucleic acids into plants are generally known in the art. Forexample, foreign DNA can be introduced into plants, using tumor-inducing(Ti) plasmid vectors. Other methods utilized for foreign DNA deliveryinvolve the use of PEG mediated protoplast transformation,electroporation, microinjection whiskers, and biolistics ormicroprojectile bombardment for direct DNA uptake. Such methods areknown in the art. (U.S. Pat. No. 5,405,765 to Vasil et al.; Bilang etal. (1991) Gene 100: 247-250; Scheid et al., (1991) MoL Gen. Genet.,228: 104-1 12; Guerche et al., (1987) Plant Science 52: 1 1 1-1 16;Neuhause et al., (1987) Theor. Appl Genet. 75: 30-36; Klein et al.,(1987) Nature 327: 70-73; Howell et al., (1980) Science 208: 1265;Horsch et al., (1985) Science 227: 1229-1231; DeBlock et al., (1989)Plant Physiology 91: 694-701; Methods for Plant Molecular Biology(Weissbach and Weissbach, eds.) Academic Press, Inc. (1988) and Methodsin Plant Molecular Biology (Schuler and Zielinski, eds.) Academic Press,Inc. (1989).

Other suitable methods of introducing nucleotide sequences into plantcells include microinjection as described by e.g., Crossway et al.(1986) Biotechniques 4:320-334, electroporation as described by e.g.,Riggs et al. (1986) Proc. Natl. Acad. ScL USA 83:5602-5606,Agrobacterium-mediated transformation as described by e.g., Townsend etal., U.S. Pat. No. 5,563,055, Zhao et al., U.S. Pat. No. 5,981,840,direct gene transfer as described by, e.g., Paszkowski et al. (1984)EMBO J. 3:2717-2722, and ballistic particle acceleration as describedby, e.g., U.S. Pat. Nos. 4,945,050; 5,879,918; 5,886,244; and 5,932,782;Tomes et al. (1995) “Direct DNA Transfer into Intact Plant Cells viaMicroprojectile Bombardment,” in Plant Cell, Tissue, and Organ Culture:Fundamental Methods, ed. Gamborg and Phillips (Springer-Verlag, Berlin);McCabe et al. (1988) Biotechnology 6:923-926); and Led transformation(WO 00/28058). Also see, Weissinger et al., (1988) Ann. Rev. Genet.22:421-477; Sanford et al, (1987) Particulate Science and Technology5:27-37 (onion); Christou et al, (1988) Plant Physiol. 87:671-674(soybean); McCabe et al., (1988) Bio/Technology 6:923-926 (soybean);Finer and McMullen (1991) In Vitro Cell Dev. Biol. 27P: 175-182(soybean); Singh et al, (1998) Theor. Appl. Genet. 96:319-324 (soybean);Datta et al., (1990) Biotechnology 8:736-740 (rice); Klein et al.,(1988) PNAS, 85:4305-4309 (maize); Klein et al., (1988) Biotechnology6:559-563 (maize); U.S. Pat. Nos. 5,240,855; 5,322,783; and 5,324,646;Tomes et al., (1995) “Direct DNA Transfer into Intact Plant Cells viaMicroprojectile Bombardment,” in Plant Cell, Tissue, and Organ Culture:Fundamental Methods, ed. Gamborg (Springer-Verlag, Berlin) (maize);Klein et al., (1988) Plant Physiol. 91:440-444 (maize); From et al.,(1990) Biotechnology 8:833-839 (maize); Hooykaas-Van Slogteren et al.,(1984) Nature (London) 31 1:763-764; Bowen et al, U.S. Pat. No.5,736,369 (cereals); Bytebier et al, (1987) PNAS 84:5345-5349(Liliaceae); De Wet et al., (1985) in The Experimental Manipulation ofOvule Tissues, ed. Chapman et al, (Longman, N.Y.), pp. 197-209 (pollen);Kaeppler et al., (1990) Plant Cell Reports 9:415-418 and Kaeppler etal., (1992) Theor. Apph Genet. 84:560-566 (whisker-mediatedtransformation); D'Halluin et al., (1992) Plant Cell 4: 1495-1505(electroporation); Li et al., (1993) Plant Cell Reports 12:250-255 andChristou and Ford (1995) Annals of Botany 75:407-413 (rice); Osjoda etal, (1996) Nature Biotechnology 14:745-750 (maize via Agrobacteriumtumefaciens); each of which is herein incorporated by reference.

Transgenic plants, including transgenic crop plants, are preferablyproduced via Agrobacterium-mediated transformation. An advantageoustransformation method is the transformation in planta. To this end, itis possible, for example, to allow the agrobacteria to act on plantseeds or to inoculate the plant meristem with agrobacteria. It hasproved particularly expedient in accordance with the invention to allowa suspension of transformed agrobacteria to act on the intact plant orat least on the flower primordia. The plant is subsequently grown onuntil the seeds of the treated plant are obtained (Clough and Bent,Plant J. (1998) 16, 735-743). Methods for Agrobacterium-mediatedtransformation of rice include well known methods for ricetransformation, such as those described in any of the following:European patent application EP 1198985 A1, Aldemita and Hodges (Planta199: 612-617, 1996); Chan et al. (Plant Mol Biol 22 (3): 491-506, 1993),Hiei et al. (Plant J 6 (2): 271-282, 1994), which disclosures areincorporated by reference herein as if fully set forth. In the case ofcorn transformation, the preferred method is as described in eitherIshida et al. (Nat. Biotechnol 14(6): 745-50, 1996) or Frame et al.(Plant Physiol 129(1): 13-22, 2002), which disclosures are incorporatedby reference herein as if fully set forth. Said methods are furtherdescribed by way of example in B. Jenes et al., Techniques for GeneTransfer, in: Transgenic Plants, Vol. 1, Engineering and Utilization,eds. S. D. Kung and R. Wu, Academic Press (1993) 128-143 and in PotrykusAnnu. Rev. Plant Physiol. Plant Molec. Biol. 42 (1991) 205-225). Thenucleic acids or the construct to be expressed is preferably cloned intoa vector, which is suitable for transforming Agrobacterium tumefaciens,for example pBin19 (Bevan et al., Nucl. Acids Res. 12 (1984) 8711).Agrobacteria transformed by such a vector can then be used in knownmanner for the transformation of plants, such as plants used as a model,like Arabidopsis (Arabidopsis thaliana is within the scope of thepresent invention not considered as a crop plant), or crop plants suchas, by way of example, tobacco plants, for example by immersing bruisedleaves or chopped leaves in an agrobacterial solution and then culturingthem in suitable media. The transformation of plants by means ofAgrobacterium tumefaciens is described, for example, by Höfgen andWillmitzer in Nucl. Acid Res. (1988) 16, 9877 or is known inter aliafrom F. F. White, Vectors for Gene Transfer in Higher Plants; inTransgenic Plants, Vol. 1, Engineering and Utilization, eds. S. D. Kungand R. Wu, Academic Press, 1993, pp. 15-38.

One transformation method known to those of skill in the art is thedipping of a flowering plant into an Agrobacteria solution, wherein theAgrobacteria contains the CESA nucleic acid, followed by breeding of thetransformed gametes. Agrobacterium mediated plant transformation can beperformed using for example the GV3101(pMP90) (Koncz and Schell, 1986,Mol. Gen. Genet. 204:383-396) or LBA4404 (Clontech) Agrobacteriumtumefaciens strain. Transformation can be performed by standardtransformation and regeneration techniques (Deblaere et al., 1994, Nucl.Acids. Res. 13:4777-4788; Gelvin, Stanton B. and Schilperoort, Robert A,Plant Molecular Biology Manual, 2nd Ed.—Dordrecht: Kluwer AcademicPubl., 1995.—in Sect., Ringbuc Zentrale Signatur: BT11-P ISBN0-7923-2731-4; Glick, Bernard R. and Thompson, John E., Methods in PlantMolecular Biology and Biotechnology, Boca Raton: CRC Press, 1993 360 S.,ISBN 0-8493-5164-2). For example, rapeseed can be transformed viacotyledon or hypocotyl transformation (Moloney et al., 1989, Plant CellReport 8:238-242; De Block et al., 1989, Plant Physiol. 91:694-701). Useof antibiotics for Agrobacterium and plant selection depends on thebinary vector and the Agrobacterium strain used for transformation.Rapeseed selection is normally performed using kanamycin as selectableplant marker. Agrobacterium mediated gene transfer to flax can beperformed using, for example, a technique described by Mlynarova et al.,1994, Plant Cell Report 13:282-285. Additionally, transformation ofsoybean can be performed using for example a technique described inEuropean Patent No. 0424 047, U.S. Pat. No. 5,322,783, European PatentNo. 0397 687, U.S. Pat. No. 5,376,543, or U.S. Pat. No. 5,169,770.Transformation of maize can be achieved by particle bombardment,polyethylene glycol mediated DNA uptake, or via the silicon carbidefiber technique. (See, for example, Freeling and Walbot “The maizehandbook” Springer Verlag: New York (1993) ISBN 3-540-97826-7). Aspecific example of maize transformation is found in U.S. Pat. No.5,990,387, and a specific example of wheat transformation can be foundin PCT Application No. WO 93/07256.

In some embodiments, polynucleotides of the present invention may beintroduced into plants by contacting plants with a virus or viralnucleic acids. Generally, such methods involve incorporating apolynucleotide construct of the invention within a viral DNA or RNAmolecule. It is recognized that the polypeptides of the invention may beinitially synthesized as part of a viral polyprotein, which later may beprocessed by proteolysis in vivo or in vitro to produce the desiredrecombinant polypeptide. Further, it is recognized that promoters of theinvention also encompass promoters utilized for transcription by viralRNA polymerases. Methods for introducing polynucleotide constructs intoplants and expressing a protein encoded therein, involving viral DNA orRNA molecules, are known in the art. See, for example, U.S. Pat. Nos.5,889,191, 5,889,190, 5,866,785, 5,589,367 and 5,316,931; hereinincorporated by reference. The cells that have been transformed may begrown into plants in accordance with conventional ways. See, forexample, McCormick et al. (1986) Plant Cell Reports 5:81-84. Theseplants may then be grown, and either pollinated with the sametransformed strain or different strains, and the resulting hybrid havingconstitutive expression of the desired phenotypic characteristicidentified. Two or more generations may be grown to ensure thatexpression of the desired phenotypic characteristic is stably maintainedand inherited and then seeds harvested to ensure expression of thedesired phenotypic characteristic has been achieved.

The present invention may be used for transformation of any plantspecies, including, but not limited to, monocots and dicots. Examples ofplant species of interest include, but are not limited to, corn or maize(Zea mays), Brassica sp. (e.g., B. napus, B. rapa, B. juncea),particularly those Brassica species useful as sources of seed oil,alfalfa (Medicago sativa), rice (Oryza sativa), rye (Secale cereale),sorghum (Sorghum bicolor, Sorghum vulgare), millet e.g., pearl millet(Pennisetum glaucum), proso millet (Panicum miliaceum), foxtail millet(Setaria italica), finger millet (Eleusine coracana)), sunflower(Helianthus annu), saffiower (Carthamus tinctorius), wheat (Triticumaestivum, T. Turgidum ssp. durum), soybean (Glycine max), tobacco(Nicotiana tabacum), potato (Solarium tuberosum), peanuts (Arachishypogaea), cotton (Gossypium barbadense, Gossypium hirsutum), sweetpotato (Ipomoea batatus), cassava (Manihot esculenta), coffee (Coffeaspp.), coconut (Cocos nucifera), pineapple (Ananas comosus), citrustrees (Citrus spp.), cocoa (Theobroma cacao), tea (Camellia sinensis),banana (Musa spp.), avocado (Persea americana), fig (Ficus casica),guava (Psidium guajava), mango (Mangifera indica), olive (Oleaeuropaea), papaya (Carica papaya), cashew (Anacardium occidentale),macadamia (Macadamia integrifolia), almond (Prunus amygdalus), sugarbeets (Beta vulgaris), sugarcane (Saccharum spp.), oats, barley,vegetables, ornamentals, and conifers. Preferably, plants of the presentinvention are crop plants (for example, sunflower, Brassica sp., cotton,sugar, beet, soybean, peanut, alfalfa, safflower, tobacco, corn, rice,wheat, rye, barley triticale, sorghum, millet, etc.).

In addition to the transformation of somatic cells, which then have tobe regenerated into intact plants, it is also possible to transform thecells of plant meristems and in particular those cells which developinto gametes. In this case, the transformed gametes follow the naturalplant development, giving rise to transgenic plants. Thus, for example,seeds of Arabidopsis are treated with agrobacteria and seeds areobtained from the developing plants of which a certain proportion istransformed and thus transgenic [Feldman, K A and Marks M D (1987). MolGen Genet 208:274-289; Feldmann K (1992). In: C Koncz, N—H Chua and JShell, Eds, Methods in Arabidopsis Research. Word Scientific, Singapore,pp. 274-289]. Alternative methods are based on the repeated removal ofthe inflorescences and incubation of the excision site in the center ofthe rosette with transformed agrobacteria, whereby transformed seeds canlikewise be obtained at a later point in time (Chang (1994). Plant J. 5:551-558; Katavic (1994). Mol Gen Genet, 245: 363-370). However, anespecially effective method is the vacuum infiltration method with itsmodifications such as the “floral dip” method. In the case of vacuuminfiltration of Arabidopsis, intact plants under reduced pressure aretreated with an agrobacterial suspension [Bechthold, N (1993). C R AcadSci Paris Life Sci, 316: 1194-1199], while in the case of the “floraldip” method the developing floral tissue is incubated briefly with asurfactant-treated agrobacterial suspension [Clough, S J and Bent A F(1998) The Plant J. 16, 735-743]. A certain proportion of transgenicseeds are harvested in both cases, and these seeds can be distinguishedfrom non-transgenic seeds by growing under the above-described selectiveconditions. In addition the stable transformation of plastids is ofadvantages because plastids are inherited maternally is most cropsreducing or eliminating the risk of transgene flow through pollen. Thetransformation of the chloroplast genome is generally achieved by aprocess which has been schematically displayed in Klaus et al., 2004[Nature Biotechnology 22 (2), 225-229]. Briefly the sequences to betransformed are cloned together with a selectable marker gene betweenflanking sequences homologous to the chloroplast genome. Thesehomologous flanking sequences direct site specific integration into theplastome. Plastidal transformation has been described for many differentplant species and an overview is given in Bock (2001) Transgenicplastids in basic research and plant biotechnology. J Mol Biol. 2001Sep. 21; 312 (3):425-38 or Maliga, P (2003) Progress towardscommercialization of plastid transformation technology. TrendsBiotechnol. 21, 20-28. Further biotechnological progress has recentlybeen reported in form of marker free plastid transformants, which can beproduced by a transient co-integrated maker gene (Klaus et al., 2004,Nature Biotechnology 22(2), 225-229). The genetically modified plantcells can be regenerated via all methods with which the skilled workeris familiar. Suitable methods can be found in the abovementionedpublications by S. D. Kung and R. Wu, Potrykus or Höfgen and Willmitzer.

Generally after transformation, plant cells or cell groupings areselected for the presence of one or more markers which are encoded byplant-expressible genes co-transferred with the gene of interest,following which the transformed material is regenerated into a wholeplant. To select transformed plants, the plant material obtained in thetransformation is, as a rule, subjected to selective conditions so thattransformed plants can be distinguished from untransformed plants. Forexample, the seeds obtained in the above-described manner can be plantedand, after an initial growing period, subjected to a suitable selectionby spraying. A further possibility consists in growing the seeds, ifappropriate after sterilization, on agar plates using a suitableselection agent so that only the transformed seeds can grow into plants.Alternatively, the transformed plants are screened for the presence of aselectable marker such as the ones described above.

Following DNA transfer and regeneration, putatively transformed plantsmay also be evaluated, for instance using Southern analysis, for thepresence of the gene of interest, copy number and/or genomicorganisation. Alternatively or additionally, expression levels of thenewly introduced DNA may be monitored using Northern and/or Westernanalysis, both techniques being well known to persons having ordinaryskill in the art.

The generated transformed plants may be propagated by a variety ofmeans, such as by clonal propagation or classical breeding techniques.For example, a first generation (or T1) transformed plant may be selfedand homozygous second-generation (or T2) transformants selected, and theT2 plants may then further be propagated through classical breedingtechniques. The generated transformed organisms may take a variety offorms. For example, they may be chimeras of transformed cells andnon-transformed cells; clonal transformants (e.g., all cells transformedto contain the expression cassette); grafts of transformed anduntransformed tissues (e.g., in plants, a transformed rootstock graftedto an untransformed scion).

Preferably, the expression of the nucleic acid in the plant results inthe plant's increased tolerance to CESA-inhibiting herbicide as comparedto a wild type variety of the plant.

In another embodiment, the invention refers to a plant, comprising aplant cell according to the present invention, wherein expression of thenucleic acid in the plant results in the plant's increased resistance toCESA-inhibiting herbicide as compared to a wild type variety of theplant.

The plants described herein can be either transgenic crop plants ornon-transgenic plants.

In addition to the general definition, give SUPRA, “transgenic”,“transgene” or “recombinant” means with regard to, for example, anucleic acid sequence, an expression cassette, gene construct or avector comprising the nucleic acid sequence or an organism transformedwith the nucleic acid sequences, expression cassettes or vectorsaccording to the invention, all those constructions brought about byrecombinant methods in which either

-   (a) the nucleic acid sequences encoding proteins useful in the    methods of the invention, or-   (b) genetic control sequence(s) which is operably linked with the    nucleic acid sequence according to the invention, for example a    promoter, or-   (c) a) and b)    are not located in their natural genetic environment or have been    modified by recombinant methods, it being possible for the    modification to take the form of, for example, a substitution,    addition, deletion, inversion or insertion of one or more nucleotide    residues in order to allow for the expression of the wildtype or    mutated CESA of the present invention. The natural genetic    environment is understood as meaning the natural genomic or    chromosomal locus in the original plant or the presence in a genomic    library. In the case of a genomic library, the natural genetic    environment of the nucleic acid sequence is preferably retained, at    least in part. The environment flanks the nucleic acid sequence at    least on one side and has a sequence length of at least 50 bp,    preferably at least 500 bp, especially preferably at least 1000 bp,    most preferably at least 5000 bp. A naturally occurring expression    cassette—for example the naturally occurring combination of the    natural promoter of the nucleic acid sequences with the    corresponding nucleic acid sequence encoding a polypeptide useful in    the methods of the present invention, as defined above—becomes a    transgenic expression cassette when this expression cassette is    modified by non-natural, synthetic (“artificial”) methods such as,    for example, mutagenic treatment. Suitable methods are described,    for example, in U.S. Pat. No. 5,565,350 or WO 00/15815.

A transgenic plant for the purposes of the invention is thus understoodas meaning, as above, that the nucleic acids of the invention are not attheir natural locus in the genome of said plant, it being possible forthe nucleic acids to be expressed homologously or heterologously.However, as mentioned, transgenic also means that, while the nucleicacids according to the invention or used in the inventive method are attheir natural position in the genome of a plant, the sequence has beenmodified with regard to the natural sequence, and/or that the regulatorysequences of the natural sequences have been modified. Transgenic ispreferably understood as meaning the expression of the nucleic acidsaccording to the invention at an unnatural locus in the genome, i.e.homologous or, preferably, heterologous expression of the nucleic acidstakes place. Preferred transgenic plants are mentioned herein.Furthermore, the term “transgenic” refers to any plant, plant cell,callus, plant tissue, or plant part, that contains all or part of atleast one recombinant polynucleotide. In many cases, all or part of therecombinant polynucleotide is stably integrated into a chromosome orstable extra-chromosomal element, so that it is passed on to successivegenerations. For the purposes of the invention, the term “recombinantpolynucleotide” refers to a polynucleotide that has been altered,rearranged, or modified by genetic engineering. Examples include anycloned polynucleotide, or polynucleotides, that are linked or joined toheterologous sequences. The term “recombinant” does not refer toalterations of polynucleotides that result from naturally occurringevents, such as spontaneous mutations, or from non-spontaneousmutagenesis followed by selective breeding.

Plants containing mutations arising due to non-spontaneous mutagenesisand selective breeding are referred to herein as non-transgenic plantsand are included in the present invention. In embodiments wherein theplant is transgenic and comprises multiple wildtype or mutated CESAnucleic acids, the nucleic acids can be derived from different genomesor from the same genome. Alternatively, in embodiments wherein the plantis non-transgenic and comprises multiple wildtype or mutated CESAnucleic acids, the nucleic acids are located on different genomes or onthe same genome.

In certain embodiments, the present invention involvesherbidicide-resistant plants that are produced by mutation breeding.Such plants comprise a polynucleotide encoding a wildtype or mutatedCESA and are tolerant to one or more CESA-inhibiting herbicides. Suchmethods can involve, for example, exposing the plants or seeds to amutagen, particularly a chemical mutagen such as, for example, ethylmethanesulfonate (EMS) and selecting for plants that have enhancedtolerance to at least one or more CESA-inhibiting herbicide [see Example1].

However, the present invention is not limited to herbicide-tolerantplants that are produced by a mutagenesis method involving the chemicalmutagen EMS. Any mutagenesis method known in the art may be used toproduce the herbicide-resistant plants of the present invention. Suchmutagenesis methods can involve, for example, the use of any one or moreof the following mutagens: radiation, such as X-rays, Gamma rays (e.g.,cobalt 60 or cesium 137), neutrons, (e.g., product of nuclear fission byuranium 235 in an atomic reactor), Beta radiation (e.g., emitted fromradioisotopes such as phosphorus 32 or carbon 14), and ultravioletradiation (preferably from 250 to 290 nm), and chemical mutagens such asbase analogues (e.g., 5-bromo-uracil), related compounds (e.g., 8-ethoxycaffeine), antibiotics (e.g., streptonigrin), alkylating agents (e.g.,sulfur mustards, nitrogen mustards, epoxides, ethylenamines, sulfates,sulfonates, sulfones, lactones), azide, hydroxylamine, nitrous acid, oracridines. Herbicide-resistant plants can also be produced by usingtissue culture methods to select for plant cells comprisingherbicide-resistance mutations and then regenerating herbicide-resistantplants therefrom. See, for example, U.S. Pat. Nos. 5,773,702 and5,859,348, both of which are herein incorporated in their entirety byreference. Further details of mutation breeding can be found in“Principals of Cultivar Development” Fehr, 1993 Macmillan PublishingCompany the disclosure of which is incorporated herein by reference

The plant of the present invention comprises at least one wildtype ormutated CESA nucleic acid or over-expressed wild-type CESA nucleic acid,and has increased tolerance to a CESA-inhibiting herbicide as comparedto a wild-type variety of the plant. It is possible for the plants ofthe present invention to have multiple wildtype or mutated CESA nucleicacids from different genomes since these plants can contain more thanone genome. For example, a plant contains two genomes, usually referredto as the A and B genomes. Because CESA is a required metabolic enzyme,it is assumed that each genome has at least one gene coding for the CESAenzyme (i.e. at least one CESA gene). As used herein, the term “CESAgene locus” refers to the position of a CESA gene on a genome, and theterms “CESA gene” and “CESA nucleic acid” refer to a nucleic acidencoding the CESA enzyme. The CESA nucleic acid on each genome differsin its nucleotide sequence from a CESA nucleic acid on another genome.One of skill in the art can determine the genome of origin of each CESAnucleic acid through genetic crossing and/or either sequencing methodsor exonuclease digestion methods known to those of skill in the art.

The present invention includes plants comprising one, two, three, ormore wildtype or mutated CESA alleles, wherein the plant has increasedtolerance to a CESA-inhibiting herbicide as compared to a wild-typevariety of the plant. The wildtype or mutated CESA alleles can comprisea nucleotide sequence selected from the group consisting of apolynucleotide as defined in SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72,73, 74, 75, 76, or 77, or a variant or derivative thereof, apolynucleotide encoding a polypeptide as defined in SEQ ID NO: 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, or 64, or a variant or derivative, homologue,orthologue, paralogue thereof, a polynucleotide comprising at least 60consecutive nucleotides of any of the aforementioned polynucleotides;and a polynucleotide complementary to any of the aforementionedpolynucleotides.

“Alleles” or “allelic variants” are alternative forms of a given gene,located at the same chromosomal position. Allelic variants encompassSingle Nucleotide Polymorphisms (SNPs), as well as SmallInsertion/Deletion Polymorphisms (INDELs). The size of INDELs is usuallyless than 100 bp. SNPs and INDELs form the largest set of sequencevariants in naturally occurring polymorphic strains of most organisms

The term “variety” refers to a group of plants within a species definedby the sharing of a common set of characteristics or traits accepted bythose skilled in the art as sufficient to distinguish one cultivar orvariety from another cultivar or variety. There is no implication ineither term that all plants of any given cultivar or variety will begenetically identical at either the whole gene or molecular level orthat any given plant will be homozygous at all loci. A cultivar orvariety is considered “true breeding” for a particular trait if, whenthe true-breeding cultivar or variety is self-pollinated, all of theprogeny contain the trait. The terms “breeding line” or “line” refer toa group of plants within a cultivar defined by the sharing of a commonset of characteristics or traits accepted by those skilled in the art assufficient to distinguish one breeding line or line from anotherbreeding line or line. There is no implication in either term that allplants of any given breeding line or line will be genetically identicalat either the whole gene or molecular level or that any given plant willbe homozygous at all loci. A breeding line or line is considered “truebreeding” for a particular trait if, when the true-breeding line orbreeding line is self-pollinated, all of the progeny contain the trait.In the present invention, the trait arises from a mutation in a CESAgene of the plant or seed.

The herbicide-resistant plants of the invention that comprisepolynucleotides encoding wildtype or mutated CESA polypeptides also finduse in methods for increasing the herbicide-resistance of a plantthrough conventional plant breeding involving sexual reproduction. Themethods comprise crossing a first plant that is a herbicide-resistantplant of the invention to a second plant that may or may not beresistant to the same herbicide or herbicides as the first plant or maybe resistant to different herbicide or herbicides than the first plant.The second plant can be any plant that is capable of producing viableprogeny plants (i.e., seeds) when crossed with the first plant.Typically, but not necessarily, the first and second plants are of thesame species. The methods can optionally involve selecting for progenyplants that comprise the wildtype or mutated CESA polypeptides of thefirst plant and the herbicide resistance characteristics of the secondplant. The progeny plants produced by this method of the presentinvention have increased resistance to a herbicide when compared toeither the first or second plant or both. When the first and secondplants are resistant to different herbicides, the progeny plants willhave the combined herbicide tolerance characteristics of the first andsecond plants. The methods of the invention can further involve one ormore generations of backcrossing the progeny plants of the first crossto a plant of the same line or genotype as either the first or secondplant. Alternatively, the progeny of the first cross or any subsequentcross can be crossed to a third plant that is of a different line orgenotype than either the first or second plant. The present inventionalso provides plants, plant organs, plant tissues, plant cells, seeds,and non-human host cells that are transformed with the at least onepolynucleotide molecule, expression cassette, or transformation vectorof the invention. Such transformed plants, plant organs, plant tissues,plant cells, seeds, and non-human host cells have enhanced tolerance orresistance to at least one herbicide, at levels of the herbicide thatkill or inhibit the growth of an untransformed plant, plant tissue,plant cell, or non-human host cell, respectively. Preferably, thetransformed plants, plant tissues, plant cells, and seeds of theinvention are Arabidopsis thaliana and crop plants.

It is to be understood that the plant of the present invention cancomprise a wild type CESA nucleic acid in addition to a mutated CESAnucleic acid. It is contemplated that the CESA-inhibiting herbicidetolerant lines may contain a mutation in only one of multiple CESAisoenzymes. Therefore, the present invention includes a plant comprisingone or more mutated CESA nucleic acids in addition to one or more wildtype CESA nucleic acids.

In another embodiment, the invention refers to a seed produced by atransgenic plant comprising a plant cell of the present invention,wherein the seed is true breeding for an increased resistance to aCESA-inhibiting herbicide as compared to a wild type variety of theseed.

In other aspects, CESA-inhibiting herbicides-tolerant plants of thepresent invention can be employed as CESA-inhibitingherbicides-tolerance trait donor lines for development, as bytraditional plant breeding, to produce other varietal and/or hybridcrops containing such trait or traits. All such resulting variety orhybrids crops, containing the ancestral CESA-inhibitingherbicides-tolerance trait or traits can be referred to herein asprogeny or descendant of the ancestral, CESA-inhibitingherbicides-tolerant line(s).

In other embodiments, the present invention provides a method forproducing a CESA-inhibiting herbicides-tolerant plant. The methodcomprises: crossing a first CESA-inhibiting herbicides-tolerant plantwith a second plant to produce a CESA-inhibiting herbicides-tolerantprogeny plant, wherein the first plant and the progeny plant comprise inat least some of their cells a polynucleotide operably linked to apromoter operable in plant cells, the recombinant polynucleotide beingeffective in the cells of the first plant to express a wildtype ormutated CESA polypeptide encoded by the polynucleotide, the expressionof the wildtype or mutated CESA polypeptide conferring to the planttolerance to CESA-inhibiting herbicides.

In some embodiments, traditional plant breeding is employed whereby theCESA-inhibiting herbicides-tolerant trait is introduced in the progenyplant resulting therefrom. In one embodiment, the present inventionprovides a method for producing a CESA-inhibiting herbicides-tolerantprogeny plant, the method comprising: crossing a parent plant with aCESA-inhibiting herbicides-tolerant plant to introduce theCESA-inhibiting herbicides-tolerance characteristics of theCESA-inhibiting herbicides-tolerant plant into the germplasm of theprogeny plant, wherein the progeny plant has increased tolerance to theCESA-inhibiting herbicides relative to the parent plant. In otherembodiments, the method further comprises the step of introgressing theCESA-inhibiting herbicides-tolerance characteristics through traditionalplant breeding techniques to obtain a descendent plant having theCESA-inhibiting herbicides-tolerance characteristics.

In other aspects, plants of the invention include those plants which, inaddition to being CESA-inhibiting herbicides-tolerant, have beensubjected to further genetic modifications by breeding, mutagenesis orgenetic engineering, e.g. have been rendered tolerant to applications ofspecific other classes of herbicides, such as AHAS inhibitors; auxinicherbicides; bleaching herbicides such as hydroxyphenylpyruvatedioxygenase (HPPD) inhibitors or phytoene desaturase (PDS) inhibitors;EPSPS inhibitors such as glyphosate; glutamine synthetase (GS)inhibitors such as glufosinate; lipid biosynthesis inhibitors such asacetyl CoA carboxylase (ACCase) inhibitors; or oxynil {i.e. bromoxynilor ioxynil) herbicides as a result of conventional methods of breedingor genetic engineering, Thus, CESA-inhibiting herbicides-tolerant plantsof the invention can be made resistant to multiple classes of herbicidesthrough multiple genetic modifications, such as resistance to bothglyphosate and glufosinate or to both glyphosate and a herbicide fromanother class such as HPPD inhibitors, AHAS inhibitors, or ACCaseinhibitors. These herbicide resistance technologies are, for example,described in Pest Management Science (at volume, year, page): 61, 2005,246; 61, 2005, 258; 61, 2005, 277; 61, 2005, 269; 61, 2005, 286; 64,2008, 326; 64, 2008, 332; Weed Science 57, 2009, 108; Australian Journalof Agricultural Research 58, 2007, 708; Science 316, 2007, 1185; andreferences quoted therein. For example, CESA-inhibitingherbicides-tolerant plants of the invention, in some embodiments, may betolerant to ACCase inhibitors, such as “dims” {e.g., cycloxydim,sethoxydim, clethodim, or tepraloxydim), “fops” {e.g., clodinafop,diclofop, fluazifop, haloxyfop, or quizalofop), and “dens” (such aspinoxaden); to auxinic herbicides, such as dicamba; to EPSPS inhibitors,such as glyphosate; to other CESA inhibitors; and to GS inhibitors, suchas glufosinate.

In addition to these classes of inhibitors, CESA-inhibitingherbicides-tolerant plants of the invention may also be tolerant toherbicides having other modes of action, for example,chlorophyll/carotenoid pigment inhibitors, cell membrane disrupters,photosynthesis inhibitors, cell division inhibitors, root inhibitors,shoot inhibitors, and combinations thereof.

Such tolerance traits may be expressed, e.g.: as mutant or wildtype HPPDproteins, as mutant AHASL proteins, mutant ACCase proteins, mutant EPSPSproteins, or mutant glutamine synthetase proteins; or as mutant native,inbred, or transgenic aryloxyalkanoate dioxygenase (AAD or DHT),haloarylnitrilase (BXN), 2,2-dichloropropionic acid dehalogenase (DEH),glyphosate-N-acetyltransferase (GAT), glyphosate decarboxylase (GDC),glyphosate oxidoreductase (GOX), glutathione-S-transferase (GST),phosphinothricin acetyltransferase (PAT or bar), or CYP450s proteinshaving an herbicide-degrading activity. CESA-inhibitingherbicides-tolerant plants hereof can also be stacked with other traitsincluding, but not limited to, pesticidal traits such as Bt Cry andother proteins having pesticidal activity toward coleopteran,lepidopteran, nematode, or other pests; nutrition or nutraceuticaltraits such as modified oil content or oil profile traits, high proteinor high amino acid concentration traits, and other trait types known inthe art.

Furthermore, in other embodiments, CESA-inhibiting herbicides-tolerantplants are also covered which are, by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for suchcharacteristics, rendered able to synthesize one or more insecticidalproteins, especially those known from the bacterial genus Bacillus,particularly from Bacillus thuringiensis, such as [delta]-endotoxins,e.g. CryIA(b), CryIA(c), CryIF, CryIF(a2), CryIIA(b), CryIIIA,CryIIIB(bl) or Cry9c; vegetative insecticidal proteins (VIP), e.g. VIP1,VIP2, VIP3 or VIP3A; insecticidal proteins of bacteria colonizingnematodes, e.g. Photorhabdus spp. or Xenorhabdus spp.; toxins producedby animals, such as scorpion toxins, arachnid toxins, wasp toxins, orother insect-specific neurotoxins; toxins produced by fungi, suchstreptomycete toxins; plant lectins, such as pea or barley lectins;agglutinins; proteinase inhibitors, such as trypsin inhibitors, serineprotease inhibitors, patatin, cystatin or papain inhibitors;ribosome-inactivating proteins (RIP), such as ricin, maize-RIP, abrin,luffin, saporin or bryodin; steroid metabolism enzymes, such as3-hydroxy-steroid oxidase, ecdysteroid-IDP-glycosyl-transferase,cholesterol oxidases, ecdysone inhibitors or HMG-CoA-reductase; ionchannel blockers, such as blockers of sodium or calcium channels;juvenile hormone esterase; diuretic hormone receptors (helicokininreceptors); stilben synthase, bibenzyl synthase, chitinases orglucanases. In the context of the present invention these insecticidalproteins or toxins are to be understood expressly also as pre-toxins,hybrid proteins, truncated or otherwise modified proteins. Hybridproteins are characterized by a new combination of protein domains,(see, e.g. WO 02/015701). Further examples of such toxins or geneticallymodified plants capable of synthesizing such toxins are disclosed, e.g.,in EP-A 374 753, WO 93/007278, WO 95/34656, EP-A 427 529, EP-A 451 878,WO 03/18810 and WO 03/52073. The methods for producing such geneticallymodified plants are generally known to the person skilled in the art andare described, e.g. in the publications mentioned above. Theseinsecticidal proteins contained in the genetically modified plantsimpart to the plants producing these proteins tolerance to harmful pestsfrom all taxonomic groups of arthropods, especially to beetles(Coeloptera), two-winged insects (Diptera), and moths (Lepidoptera) andto nematodes (Nematoda).

In some embodiments, expression of one or more protein toxins (e.g.,insecticidal proteins) in the CESA-inhibiting herbicides-tolerant plantsis effective for controlling organisms that include, for example,members of the classes and orders: Coleoptera such as the American beanweevil Acanthoscelides obtectus; the leaf beetle Agelastica alni; clickbeetles (Agriotes lineatus, Agriotes obscurus, Agriotes bicolor); thegrain beetle Ahasverus advena; the summer schafer Amphimallonsolstitialis; the furniture beetle Anobium punctatum; Anthonomus spp.(weevils); the Pygmy mangold beetle Atomaria linearis; carpet beetles(Anthrenus spp., Attagenus spp.); the cowpea weevil Callosobruchusmaculates; the fried fruit beetle Carpophilus hemipterus; the cabbageseedpod weevil Ceutorhynchus assimilis; the rape winter stem weevilCeutorhynchus picitarsis; the wireworms Conoderus vespertinus andConoderus falli; the banana weevil Cosmopolites sordidus; the NewZealand grass grub Costelytra zealandica; the June beetle Cotinisnitida; the sunflower stem weevil

Cylindrocopturus adspersus; the larder beetle Dermestes lardarius; thecorn rootworms Diabrotica virgifera, Diabrotica virgifera virgifera, andDiabrotica barberi; the Mexican bean beetle Epilachna varivestis; theold house borer Hylotropes bajulus; the lucerne weevil Hypera postica;the shiny spider beetle Gibbium psylloides; the cigarette beetleLasioderma serricorne; the Colorado potato beetle Leptinotarsadecemlineata; Lyctus beetles {Lyctus spp., the pollen beetle Meligethesaeneus; the common cockshafer Melolontha melolontha; the American spiderbeetle Mezium americanum; the golden spider beetle Niptus hololeucs; thegrain beetles Oryzaephilus surinamensis and Oryzaephilus Mercator; theblack vine weevil Otiorhynchus sulcatus; the mustard beetle Phaedoncochleariae, the crucifer flea beetle Phyllotreta cruciferae; thestriped flea beetle Phyllotreta striolata; the cabbage steam flea beetlePsylliodes chrysocephala; Ptinus spp. (spider beetles); the lesser grainborer Rhizopertha dominica; the pea and been weevil Sitona lineatus; therice and granary beetles Sitophilus oryzae and Sitophilus granaries; thered sunflower seed weevil Smicronyx fulvus; the drugstore beetleStegobium paniceum; the yellow mealworm beetle Tenebrio molitor, theflour beetles Tribolium castaneum and Tribolium confusum; warehouse andcabinet beetles {Trogoderma spp.); the sunflower beetle Zygogrammaexclamationis; Dermaptera (earwigs) such as the European earwigForficula auricularia and the striped earwig Labidura riparia;Dictyoptera such as the oriental cockroach Blatta orientalis; thegreenhouse millipede Oxidus gracilis; the beet fly Pegomyia betae; thefrit fly Oscinella frit; fruitflies (Dacus spp., Drosophila spp.);Isoptera (termites) including species from the familes Hodotermitidae,Kalotermitidae, Mastotermitidae, Rhinotermitidae, Serritermitidae,Termitidae, Termopsidae; the tarnished plant bug Lygus lineolaris; theblack bean aphid Aphis fabae; the cotton or melon aphid Aphis gossypii;the green apple aphid Aphis pomi; the citrus spiny whiteflyAleurocanthus spiniferus; the sweet potato whitefly Bemesia tabaci; thecabbage aphid Brevicoryne brassicae; the pear psylla Cacopsyllapyricola; the currant aphid Cryptomyzus ribis; the grape phylloxeraDaktulosphaira vitifoliae; the citrus psylla Diaphorina citri; thepotato leafhopper Empoasca fabae; the bean leafhopper Empoasca Solana;the vine leafhopper Empoasca vitis; the woolly aphid Eriosoma lanigerum;the European fruit scale Eulecanium corni; the mealy plum aphidHyalopterus arundinis; the small brown planthopper Laodelphaxstriatellus; the potato aphid Macrosiphum euphorbiae; the green peachaphid Myzus persicae; the green rice leafhopper Nephotettix cinticeps;the brown planthopper Nilaparvata lugens; the hop aphid Phorodon humuli;the bird-cherry aphid Rhopalosiphum padi; the grain aphid Sitobionavenae; Lepidoptera such as Adoxophyes orana (summer fruit tortrixmoth); Archips podana (fruit tree tortrix moth); Bucculatrix pyrivorella(pear leafminer); Bucculatrix thurberiella (cotton leaf perforator);Bupalus piniarius (pine looper); Carpocapsa pomonella (codling moth);Chilo suppressalis (striped rice borer); Choristoneura fumiferana(eastern spruce budworm); Cochylis hospes (banded sunflower moth);Diatraea grandiosella (southwestern corn borer); Eupoecilia ambiguella(European grape berry moth); Helicoverpa armigera (cotton bollworm);Helicoverpa zea (cotton bollworm); Heliothis vires cens (tobaccobudworm), Homeosoma electellum (sunflower moth); Homona magnanima(oriental tea tree tortrix moth); Lithocolletis blancardella (spottedtentiform leafminer); Lymantria dispar (gypsy moth); Malacosoma neustria(tent caterpillar); Mamestra brassicae (cabbage armyworm); Mamestraconfigurata (Bertha armyworm); Operophtera brumata (winter moth);Ostrinia nubilalis (European corn borer), Panolis flammea (pine beautymoth), Phyllocnistis citrella (citrus leafminer); Pieris brassicae(cabbage white butterfly); Rachiplusia ni (soybean looper); Spodopteraexigua (beet armywonn); Spodoptera littoralis (cotton leafworm); Syleptaderogata (cotton leaf roller); Trichoplusia ni (cabbage looper);Orthoptera such as the common cricket Acheta domesticus, tree locusts(Anacridium spp.), the migratory locust Locusta migratoria, thetwostriped grasshopper Melanoplus bivittatus, the differentialgrasshopper Melanoplus differ entialis, the redlegged grasshopperMelanoplus femurrubrum, the migratory grasshopper Melanoplussanguinipes, the northern mole cricket Neocurtilla hexadectyla, the redlocust Nomadacris septemfasciata, the shortwinged mole cricketScapteriscus abbreviatus, the southern mole cricket Scapteriscusborellii, the tawny mole cricket Scapteriscus vicinus, and the desertlocust Schistocerca gregaria; Symphyla such as the garden symphylanScutigerella immaculata; Thysanoptera such as the tobacco thripsFrankliniella fusca, the flower thrips Frankliniella intonsa, thewestern flower thrips Frankliniella occidentalism the cotton bud thripsFrankliniella schultzei, the banded greenhouse thrips Hercinothripsfemoralis, the soybean thrips Neohydatothrips variabilis, Kelly's citrusthrips Pezothrips kellyanus, the avocado thrips Scirtothrips perseae,the melon thrips Thrips palmi, and the onion thrips Thrips tabaci; andthe like, and combinations comprising one or more of the foregoingorganisms.

In some embodiments, expression of one or more protein toxins (e.g.,insecticidal proteins) in the CESA-inhibiting herbicides-tolerant plantsis effective for controlling flea beetles, i.e. members of the fleabeetle tribe of family Chrysomelidae, preferably against Phyllotretaspp., such as Phyllotreta cruciferae and/or Phyllotreta triolata. Inother embodiments, expression of one or more protein toxins {e.g.,insecticidal proteins) in the CESA-inhibiting herbicides-tolerant plantsis effective for controlling cabbage seedpod weevil, the Berthaarmyworm, Lygus bugs, or the diamondback moth.

Furthermore, in one embodiment, CESA-inhibiting herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,rendered able to synthesize one or more proteins to increase theresistance or tolerance of those plants to bacterial, viral or fungalpathogens. The methods for producing such genetically modified plantsare generally known to the person skilled in the art.

Furthermore, in another embodiment, CESA-inhibiting herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,rendered able to synthesize one or more proteins to increase theproductivity (e.g. oil content), tolerance to drought, salinity or othergrowth-limiting environmental factors or tolerance to pests and fungal,bacterial or viral pathogens of those plants.

Furthermore, in other embodiments, CESA-inhibiting herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,altered to contain a modified amount of one or more substances or newsubstances, for example, to improve human or animal nutrition, e.g. oilcrops that produce health-promoting long-chain omega-3 fatty acids orunsaturated omega-9 fatty acids (e.g. Nexera® rape, Dow Agro Sciences,Canada).

Furthermore, in some embodiments, CESA-inhibiting herbicides-tolerantplants are also covered which are, e.g. by the use of recombinant DNAtechniques and/or by breeding and/or otherwise selected for such traits,altered to contain increased amounts of vitamins and/or minerals, and/orimproved profiles of nutraceutical compounds.

In one embodiment, CESA-inhibiting herbicides-tolerant plants of thepresent invention, relative to a wild-type plant, comprise an increasedamount of, or an improved profile of, a compound selected from the groupconsisting of: glucosinolates (e.g., glucoraphanin(4-methylsulfinylbutyl-glucosinolate), sulforaphane,3-indolylmethyl-glucosinolate(glucobrassicin),I-methoxy-3-indolylmethyl-glucosinolate (neoglucobrassicin)); phenolics(e.g., flavonoids (e.g., quercetin, kaempferol), hydroxycinnamoylderivatives (e.g., 1,2,2′-trisinapoylgentiobiose,1,2-diferuloylgentiobiose, I,2′-disinapoyl-2-feruloylgentiobiose,3-O-caffeoyl-quinic (neochlorogenic acid)); and vitamins and minerals(e.g., vitamin C, vitamin E, carotene, folic acid, niacin, riboflavin,thiamine, calcium, iron, magnesium, potassium, selenium, and zinc).

In another embodiment, CESA-inhibiting herbicides-tolerant plants of thepresent invention, relative to a wild-type plant, comprise an increasedamount of, or an improved profile of, a compound selected from the groupconsisting of: progoitrin; isothiocyanates; indoles (products ofglucosinolate hydrolysis); glutathione; carotenoids such asbeta-carotene, lycopene, and the xanthophyll carotenoids such as luteinand zeaxanthin; phenolics comprising the flavonoids such as theflavonols (e.g. quercetin, rutin), the flavans/tannins (such as theprocyanidins comprising coumarin, proanthocyanidins, catechins, andanthocyanins); flavones; phytoestrogens such as coumestans, lignans,resveratrol, isoflavones e.g. genistein, daidzein, and glycitein;resorcyclic acid lactones; organosulphur compounds; phytosterols;terpenoids such as carnosol, rosmarinic acid, glycyrrhizin and saponins;chlorophyll; chlorphyllin, sugars, anthocyanins, and vanilla.

In other embodiments, CESA-inhibiting herbicides-tolerant plants of thepresent invention, relative to a wild-type plant, comprise an increasedamount of, or an improved profile of, a compound selected from the groupconsisting of: vincristine, vinblastine, taxanes (e.g., taxol(paclitaxel), baccatin III, 10-desacetylbaccatin III, 10-desacetyltaxol, xylosyl taxol, 7-epitaxol, 7-epibaccatin III,10-desacetylcephalomannine, 7-epicephalomannine, taxotere,cephalomannine, xylosyl cephalomannine, taxagifine, 8-benxoyloxytaxagifine, 9-acetyloxy taxusin, 9-hydroxy taxusin, taiwanxam, taxaneIa, taxane Ib, taxane Ic, taxane Id, GMP paclitaxel, 9-dihydro13-acetylbaccatin III, 10-desacetyl-7-epitaxol, tetrahydrocannabinol(THC), cannabidiol (CBD), genistein, diadzein, codeine, morphine,quinine, shikonin, ajmalacine, serpentine, and the like.

In other aspects, a method for treating a plant of the present inventionis provided.

In some embodiments, the method comprises contacting the plant with anagronomically acceptable composition. In one embodiment, theagronomically acceptable composition comprises a CESA inhibitingherbicide A. I, such as an azine as described herein.

In another aspect, the present invention provides a method for preparinga descendent seed. The method comprises planting a seed of or capable ofproducing a plant of the present invention. In one embodiment, themethod further comprises growing a descendent plant from the seed; andharvesting a descendant seed from the descendent plant. In otherembodiments, the method further comprises applying a CESA-inhibitingherbicides herbicidal composition to the descendent plant.

In another embodiment, the invention refers to harvestable parts of theplant according to the present invention. Preferably, the harvestableparts comprise the CESA nucleic acid or CESA protein of the presentinvention. The harvestable parts may be seeds, roots, leaves and/orflowers comprising the CESA nucleic acid or CESA protein or partsthereof. Preferred parts of soy plants are soy beans comprising the CESAnucleic acid or CESA protein.

In another embodiment, the invention refers to products derived from aplant according to the present invention, parts thereof or harvestableparts thereof. A preferred plant product is fodder, seed meal, oil, orseed-treatment-coated seeds. Preferably, the meal and/or oil comprisethe CESA nucleic acids or CESA proteins.

In another embodiment, the invention refers to a method for theproduction of a product, which method comprises

-   a) growing the plants of the invention or obtainable by the methods    of invention and-   b) producing said product from or by the plants of the invention    and/or parts, e.g. seeds, of these plants.

In a further embodiment the method comprises the steps

-   a) growing the plants of the invention,-   b) removing the harvestable parts as defined above from the plants    and-   c) producing said product from or by the harvestable parts of the    invention.

The product may be produced at the site where the plant has been grown,the plants and/or parts thereof may be removed from the site where theplants have been grown to produce the product. Typically, the plant isgrown, the desired harvestable parts are removed from the plant, iffeasible in repeated cycles, and the product made from the harvestableparts of the plant. The step of growing the plant may be performed onlyonce each time the methods of the invention is performed, while allowingrepeated times the steps of product production e.g. by repeated removalof harvestable parts of the plants of the invention and if necessaryfurther processing of these parts to arrive at the product. It is alsopossible that the step of growing the plants of the invention isrepeated and plants or harvestable parts are stored until the productionof the product is then performed once for the accumulated plants orplant parts. Also, the steps of growing the plants and producing theproduct may be performed with an overlap in time, even simultaneously toa large extend or sequentially. Generally the plants are grown for sometime before the product is produced.

In one embodiment the products produced by said methods of the inventionare plant products such as, but not limited to, a foodstuff, feedstuff,a food supplement, feed supplement, fiber, cosmetic and/orpharmaceutical. Foodstuffs are regarded as compositions used fornutrition and/or for supplementing nutrition. Animal feedstuffs andanimal feed supplements, in particular, are regarded as foodstuffs.

In another embodiment the inventive methods for the production are usedto make agricultural products such as, but not limited to, plantextracts, proteins, amino acids, carbohydrates, fats, oils, polymers,vitamins, and the like.

It is possible that a plant product consists of one or more agriculturalproducts to a large extent.

Herbicides

As described above, the present invention provides nucleic acids,polypeptides, conferring tolerance of plants to compounds/herbicidesinterfering or inhibiting cell wall (cellulose) biosynthesis byinterfering with the activity of cellulose synthase (“CESA-inhibitingherbicides”), also known to the person skilled in the art as CelluloseBiosynthesis Inhibitors (CBI).

Examples of herbicides which can be used according to the presentinvention, i.e. to which the plants according to the present inventionare tolerant/resistant to, are compounds known to the skilled artisan asazines. Examples of Azines are described in detail in the followingpatent applications depicted in the following Table 1, which areincorporated by reference in its entirety.

TABLE 1 Publication or Application number/Internal No.: StructuralFormula reference  1

WO 2014/ 064094 PF74283 I  2

WO 2015/ 007711 PF75365 (I)  3

PCT/EP2015/ 056711 PF76068 (I)  4

EP 14163356.0 PF76069 (I)  5

EP 14163742.1 PF76635 (I)  6

EP 14163743.9 PF76636 (I)  7

EP 14165565.4 PF76857  8

EP 14165624.9 PF76888  9

EP 14164431.0 PF76890 10

EP 14164434.4 PF76930 11

EP 14164433.6 PF77027 (I) 12

Indaziflam 13

Triazofenamid

Examples of preferred CESA inhibiting herbicides from the group ofso-called azines which can be used according to the present inventionare compounds having the Formula (I), known to the skilled artisan asazines.

wherein

-   A is phenyl, which is substituted by two to five substituents    selected from the group consisting of halogen, CN, NO₂, C₁-C₆-alkyl,    C₁-C₆-haloalkyl, C₂-C₆-alkenyl, C₂-C₆-haloalkenyl, C₂-C₆-alkynyl,    C₁-C₆-haloalkynyl, OH, C₁-C₆-alkoxy, C₁-C₆-alkylthio,    (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl, amino,    (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl,    (C₁-C₆-alkoxy)carbonyl;-   R¹ H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,    C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl, (C₁-C₆-alkoxy)carbonyl,    (C₁-C₆-alkyl)sulfonyl or phenylsulfonyl,    -   wherein the phenyl is unsubstituted or substituted by one to        five substituents selected from the group consisting of halogen,        CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl and C₁-C₆-alkoxy;-   R² H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl,    C₃-C₆-alkynyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, OH,    C₁-C₆-alkoxy or C₁-C₆-alkoxy-C₁-C₆-alkyl;-   R³ H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl or C₁-C₆-alkoxy;-   R⁴ H, halogen, CN, C₁-C₆-alkyl or C₁-C₆-haloalkyl; or-   R³ and R⁴ together with the carbon atom to which they are attached    form a moiety selected from the group consisting of carbonyl,    C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl and three- to    six-membered heterocyclyl,    -   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, or three- to        six-membered heterocyclyl is unsubstituted or substituted by one        to three substituents selected from halogen, CN, C₁-C₆-alkyl and        C₁-C₆-alkoxy; and-   R⁵ H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,    C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl, (C₁-C₆-alkoxy)carbonyl,    (C₁-C₆-alkyl)sulfonyl or phenylsulfonyl,    -   wherein the phenyl is unsubstituted or substituted by one to        five substituents selected from the group consisting of halogen,        CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl and C₁-C₆-alkoxy;        including their agriculturally acceptable salts or N-oxides.

Preferably the present invention provides azines of formula (I), wherein

-   -   A is 2-fluoro-phenyl, which is substituted by one to four        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)carbonyl and (C₁-C₆-alkoxy)-carbonyl;    -   R¹ H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,        C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl or phenylsulfonyl,        -   wherein the phenyl is unsubstituted or substituted by one to            five substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl and            C₁-C₆-alkoxy;    -   R² H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₂-C₆-alkenyl,        C₃-C₆-alkynyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, OH,        C₁-C₆-alkoxy or C₁-C₆-alkoxy-C₁-C₆-alkyl;    -   R³ H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl or C₁-C₆-alkoxy;    -   R⁴ H, halogen, CN, C₁-C₆-alkyl or C₁-C₆-haloalkyl; or    -   R³ and R⁴ together with the carbon atom to which they are        attached form a moiety selected from the group consisting of        carbonyl, C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl        and three- to six-membered heterocyclyl,        -   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl or and            three- to six-membered heterocyclyl is unsubstituted or            substituted by one to three substituents selected from            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy; and    -   R⁵ H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl,        C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl or phenylsulfonyl,        -   wherein the phenyl is unsubstituted or substituted by one to            five substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl and            C₁-C₆-alkoxy;    -   including their agriculturally acceptable salts or N-oxides.

Useful for the present invention are also agrochemical compositionscomprising at least one azines of formula (I) and auxiliaries customaryfor formulating crop protection agents.

The present invention also provides the use of azines of formula (I) asherbicides, i.e. for controlling harmful plants.

If the azines of formula (I) as described herein are capable of forminggeometrical isomers, for example E/Z isomers, it is possible to useboth, the pure isomers and mixtures thereof, in the compositionsaccording to the invention.

If the azines of formula (I) as described herein have one or morecentres of chirality and, as a consequence, are present as enantiomersor diastereomers, it is possible to use both, the pure enantiomers anddiastereomers and their mixtures, in the compositions according to theinvention.

If the azines of formula (I) as described herein have ionizablefunctional groups, they can also be employed in the form of theiragriculturally acceptable salts. Suitable are, in general, the salts ofthose cations and the acid addition salts of those acids whose cationsand anions, respectively, have no adverse effect on the activity of theactive compounds.

Preferred cations are the ions of the alkali metals, preferably oflithium, sodium and potassium, of the alkaline earth metals, preferablyof calcium and magnesium, and of the transition metals, preferably ofmanganese, copper, zinc and iron, further ammonium and substitutedammonium in which one to four hydrogen atoms are replaced byC₁-C₄-alkyl, hydroxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl,hydroxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, phenyl or benzyl, preferably ammonium,methylammonium, isopropylammonium, dimethylammonium,diisopropylammonium, trimethylammonium, heptylammonium, dodecylammonium,tetradecylammonium, tetramethylammonium, tetraethylammonium,tetrabutylammonium, 2-hydroxyethylammonium (olamine salt),2-(2-hydroxyeth-1-oxy)eth-1-ylammonium (diglycolamine salt),di(2-hydroxyeth-1-yl)ammonium (diolamine salt),tris(2-hydroxyethyl)ammonium (trolamine salt),tris(2-hydroxypropyl)ammonium, benzyltrimethylammonium,benzyltriethylammonium, N,N,N-trimethylethanolammonium (choline salt),furthermore phosphonium ions, sulfonium ions, preferablytri(C₁-C₄-alkyl)sulfonium, such as trimethylsulfonium, and sulfoxoniumions, preferably tri(C₁-C₄-alkyl)sulfoxonium, and finally the salts ofpolybasic amines such as N,N-bis-(3-aminopropyl)methylamine anddiethylenetriamine.

Anions of useful acid addition salts are primarily chloride, bromide,fluoride, iodide, hydrogensulfate, methylsulfate, sulfate,dihydrogenphosphate, hydrogenphosphate, nitrate, bicarbonate, carbonate,hexafluorosilicate, hexafluorophosphate, benzoate and also the anions ofC₁-C₄-alkanoic acids, preferably formate, acetate, propionate andbutyrate.

The organic moieties mentioned in the definition of the variables, e.g.R¹ to R⁵, are—like the term halogen—collective terms for individualenumerations of the individual group members. The term halogen denotesin each case fluorine, chlorine, bromine or iodine. All hydrocarbonchains, i.e. all alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, alkylthio,alkylsulfinyl, alkylsulfonyl, (alkyl)amino, di(alkyl)amino chains can bestraight-chain or branched, the prefix C_(n)-C_(m) denoting in each casethe possible number of carbon atoms in the group.

Examples of such meanings are:

-   -   C₁-C₄-alkyl: for example CH₃, C₂H₅, n-propyl, CH(CH₃)₂, n-butyl,        CH(CH₃)C₂H₅, CH₂—CH(CH₃)₂ and C(CH₃)₃;    -   C₁-C₆-alkyl and also the C₁-C₆-alkyl moieties of        (C₁-C₆-alkyl)carbonyl, C₁-C₆-alkyoxy-C₁-C₆-alkyl: C₁-C₄-alkyl as        mentioned above, and also, for example, n-pentyl, 1-methylbutyl,        2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl,        n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl,        2-methylpentyl, 3-methylpentyl, 4-methylpentyl,        1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,        2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl,        1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl,        1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or        1-ethyl-2-methylpropyl, preferably methyl, ethyl, n-propyl,        1-methylethyl, n-butyl, 1,1-dimethylethyl, n-pentyl or n-hexyl;    -   C₁-C₄-haloalkyl: a C₁-C₄-alkyl radical as mentioned above which        is partially or fully substituted by fluorine, chlorine, bromine        and/or iodine, for example, chloromethyl, dichloromethyl,        trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,        chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl,        bromomethyl, iodomethyl, 2-fluoroethyl, 2-chloroethyl,        2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl,        2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,        2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,        2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl,        3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl,        2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl,        2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl,        3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl,        heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl,        1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl,        4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, nonafluorobutyl,        1,1,2,2,-tetrafluoroethyl and        1-trifluoromethyl-1,2,2,2-tetrafluoroethyl;    -   C₁-C₆-haloalkyl: C₁-C₄-haloalkyl as mentioned above, and also,        for example, 5-fluoropentyl, 5-chloropentyl, 5-bromopentyl,        5-iodopentyl, undecafluoropentyl, 6-fluorohexyl, 6-chlorohexyl,        6-bromohexyl, 6-iodohexyl and dodecafluorohexyl;    -   C₃-C₆-cycloalkyl: monocyclic saturated hydrocarbons having 3 to        6 ring members, such as cyclopropyl, cyclobutyl, cyclopentyl and        cyclohexyl;    -   C₂-C₆-alkenyl: for example ethenyl, 1-propenyl, 2-propenyl,        1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl,        1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl,        2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl,        4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl,        3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl,        3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl,        3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl,        1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl,        1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl,        3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl,        2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl,        1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl,        4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl,        3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl,        2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl,        1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl,        1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl,        1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl,        1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl,        2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl,        2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl,        3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl,        1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,        2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl,        1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl,        1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl;    -   C₃-C₆-cycloalkenyl: 1-cyclopropenyl, 2-cyclopropenyl,        1-cyclobutenyl, 2-cyclobutenyl, 1-cyclopentenyl,        2-cyclopentenyl, 1,3-cyclopentadienyl, 1,4-cyclopentadienyl,        2,4-cyclopentadienyl, 1-cyclohexenyl, 2-cyclohexenyl,        3-cyclohexenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl,        2,5-cyclohexadienyl;    -   C₃-C₆-alkynyl: for example 1-propynyl, 2-propynyl, 1-butynyl,        2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl,        2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl,        1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl,        1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl,        2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl,        1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl,        2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl,        4-methyl-1-pentynyl, 4-methyl-2-pentynyl,        1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl,        1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl,        3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl,        2-ethyl-3-butynyl and 1-ethyl-1-methyl-2-propynyl;    -   C₁-C₄-alkoxy: for example methoxy, ethoxy, propoxy,        1-methylethoxy butoxy, 1-methylpropoxy, 2-methylpropoxy and        1,1-dimethylethoxy;    -   C₁-C₆-alkoxy and also the C₁-C₆-alkoxy moieties of        (C₁-C₆-alkoxy)carbonyl, C₁-C₆-alkoxy-C₁-C₆-alkyl: C₁-C₄-alkoxy        as mentioned above, and also, for example, pentoxy,        1-methylbutoxy, 2-methylbutoxy, 3-methoxylbutoxy,        1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy,        1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy,        3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy,        1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy,        2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy,        2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy,        1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy.    -   C₁-C₄-alkylthio: for example methylthio, ethylthio, propylthio,        1-methylethylthio, butylthio, 1-methylpropylthio,        2-methylpropylthio and 1,1-dimethylethylthio;    -   C₁-C₆-alkylthio: C₁-C₄-alkylthio as mentioned above, and also,        for example, pentylthio, 1-methylbutylthio, 2-methylbutylthio,        3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio,        hexylthio, 1,1-dimethylpropylthio, 1,2-dimethylpropylthio,        1-methylpentylthio, 2-methylpentylthio, 3-methylpentylthio,        4-methylpentylthio, 1,1-dimethylbutylthio,        1,2-dimethylbutylthio, 1,3-dimethylbutylthio,        2,2-dimethylbutylthio, 2,3-dimethylbutylthio,        3,3-dimethylbutylthio, 1-ethylbutylthio, 2-ethylbutylthio,        1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio,        1-ethyl-1-methylpropylthio and 1-ethyl-2-methylpropylthio;    -   C₁-C₆-alkylsulfinyl (C₁-C₆-alkyl-S(═O)—): z.B. methylsulfinyl,        ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl,        butylsulfinyl, 1-methylpropylsulfinyl, 2-methylpropylsulfinyl,        1,1-di-methylethylsulfinyl, pentylsulfinyl,        1-methylbutylsulfinyl, 2-methylbutylsulfinyl,        3-methylbutylsulfinyl, 2,2-dimethylpropylsulfinyl,        1-ethylpropylsulfinyl, 1,1-dimethylpropylsulfinyl,        1,2-dimethylpropylsulfinyl, hexylsulfinyl,        1-methylpentylsulfinyl, 2-methylpentylsulfinyl,        3-methylpentylsulfinyl, 4-methylpentyl-sulfinyl,        1,1-dimethylbutyl-sulfinyl, 1,2-dimethylbutylsulfinyl,        1,3-dimethylbutyl-sulfinyl, 2,2-dimethylbutylsulfinyl,        2,3-dimethylbutylsulfinyl, 3,3-dimethylbutyl-sulfinyl,        1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl,        1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl,        1-ethyl-1-methylpropylsulfinyl and        1-ethyl-2-methylpropylsulfinyl;    -   C₁-C₆-alkylsulfonyl (C₁-C₆-alkyl-S(O)₂—): for example        methylsulfonyl, ethylsulfonyl, propylsulfonyl,        1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl,        2-methylpropylsulfonyl, 1,1-dimethylethylsulfonyl,        pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl,        3-methylbutylsulfonyl, 1,1-dimethylpropylsulfonyl,        1,2-dimethylpropylsulfonyl, 2,2-dimethylpropylsulfonyl,        1-ethylpropylsulfonyl, hexylsulfonyl, 1-methylpentylsulfonyl,        2-methylpentylsulfonyl, 3-methylpentylsulfonyl,        4-methylpentylsulfonyl, 1,1-dimethylbutylsulfonyl,        1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl,        2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl,        3,3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl,        2-ethylbutylsulfonyl, 1,1,2-trimethyl-propylsulfonyl,        1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl        and 1-ethyl-2-methylpropylsulfonyl;    -   (C₁-C₄-alkyl)amino: for example methylamino, ethylamino,        propylamino, 1-methylethyl-amino, butylamino,        1-methylpropylamino, 2-methylpropylamino or        1,1-dimethylethylamino;    -   (C₁-C₆-alkyl)amino: (C₁-C₄-alkylamino) as mentioned above, and        also, for example, pentylamino, 1-methylbutylamino,        2-methylbutylamino, 3-methylbutylamino, 2,2-dimethylpropylamino,        1-ethylpropylamino, hexylamino, 1,1-dimethylpropylamino,        1,2-dimethylpropylamino, 1-methylpentylamino,        2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino,        1,1-dimethylbutylamino, 1,2-dimethylbutylamino,        1,3-dimethylbutylamino, 2,2-dimethylbutylamino,        2,3-dimethylbutyl-amino 3,3-dimethylbutyl-amino,        1-ethylbutylamino, 2-ethylbutylamino,        1,1,2-trimethylpropylamino, 1,2,2-trimethylpropylamino,        1-ethyl-1-methylpropylamino or 1-ethyl-2-methylpropylamino;    -   di(C₁-C₄-alkyl)amino: for example N,N-dimethylamino,        N,N-diethylamino, N,N-di(1-methylethyl)amino, N,N-dipropylamino,        N,N-dibutylamino, N,N-di(1-methylpropyl)amino,        N,N-di(2-methylpropyl)amino, N,N-di(1,1-dimethylethyl)amino,        N-ethyl-N-methylamino, N-methyl-N-propylamino,        N-methyl-N-(1-methylethyl)amino, N-butyl-N-methylamino,        N-methyl-N-(1-methylpropyl)amino,        N-methyl-N-(2-methylpropyl)amino,        N-(1,1-dimethylethyl)-N-methylamino, N-ethyl-N-propylamino,        N-ethyl-N-(1-methylethyl)amino, N-butyl-N-ethylamino,        N-ethyl-N-(1-methylpropyl)amino,        N-ethyl-N-(2-methylpropyl)amino,        N-ethyl-N-(1,1-dimethylethyl)amino,        N-(1-methylethyl)-N-propylamino, N-butyl-N-propylamino,        N-(1-methylpropyl)-N-propylamino,        N-(2-methylpropyl)-N-propylamino,        N-(1,1-dimethylethyl)-N-propylamino,        N-butyl-N-(1-methylethyl)amino,        N-(1-methylethyl)-N-(1-methylpropyl)amino,        N-(1-methylethyl)-N-(2-methylpropyl)amino,        N-(1,1-dimethylethyl)-N-(1-methylethyl)amino,        N-butyl-N-(1-methylpropyl)amino,        N-butyl-N-(2-methylpropyl)amino,        N-butyl-N-(1,1-dimethylethyl)amino,        N-(1-methylpropyl)-N-(2-methylpropyl)amino,        N-(1,1-dimethylethyl)-N-(1-methylpropyl)amino or        N-(1,1-dimethylethyl)-N-(2-methylpropyl)amino;    -   di(C₁-C₆-alkyl)amino: di(C₁-C₄-alkyl)amino as mentioned above,        and also, for example, N-methyl-N-pentylamino,        N-methyl-N-(1-methylbutyl)amino,        N-methyl-N-(2-methylbutyl)amino,        N-methyl-N-(3-methylbutyl)amino,        N-methyl-N-(2,2-dimethylpropyl)amino,        N-methyl-N-(1-ethylpropyl)amino, N-methyl-N-hexylamino,        N-methyl-N-(1,1-dimethylpropyl)amino,        N-methyl-N-(1,2-dimethylpropyl)amino,        N-methyl-N-(1-methylpentyl)amino,        N-methyl-N-(2-methylpentyl)amino,        N-methyl-N-(3-methylpentyl)amino,        N-methyl-N-(4-methylpentyl)amino,        N-methyl-N-(1,1-dimethylbutyl)amino,        N-methyl-N-(1,2-dimethylbutyl)amino,        N-methyl-N-(1,3-dimethylbutyl)amino,        N-methyl-N-(2,2-dimethyl-butyl)amino,        N-methyl-N-(2,3-dimethylbutyl)amino,        N-methyl-N-(3,3-dimethylbutyl)amino,        N-methyl-N-(1-ethylbutyl)amino, N-methyl-N-(2-ethylbutyl)amino,        N-methyl-N-(1,1,2-trimethylpropyl)amino,        N-methyl-N-(1,2,2-trimethylpropyl)amino,        N-methyl-N-(1-ethyl-1-methylpropyl)amino,        N-methyl-N-(1-ethyl-2-methylpropyl)amino, N-ethyl-N-pentylamino,        N-ethyl-N-(1-methylbutyl)amino, N-ethyl-N-(2-methylbutyl)amino,        N-ethyl-N-(3-methylbutyl)amino,        N-ethyl-N-(2,2-dimethylpropyl)amino,        N-ethyl-N-(1-ethylpropyl)amino, N-ethyl-N-hexylamino,        N-ethyl-N-(1,1-dimethylpropyl)amino,        N-ethyl-N-(1,2-dimethylpropyl)-amino,        N-ethyl-N-(1-methylpentyl)amino,        N-ethyl-N-(2-methylpentyl)amino,        N-ethyl-N-(3-methylpentyl)amino,        N-ethyl-N-(4-methylpentyl)amino,        N-ethyl-N-(1,1-dimethylbutyl)amino,        N-ethyl-N-(1,2-dimethylbutyl)amino,        N-ethyl-N-(1,3-dimethylbutyl)amino,        N-ethyl-N-(2,2-dimethylbutyl)amino,        N-ethyl-N-(2,3-dimethylbutyl)amino,        N-ethyl-N-(3,3-dimethylbutyl)amino,        N-ethyl-N-(1-ethylbutyl)amino, N-ethyl-N-(2-ethylbutyl)amino,        N-ethyl-N-(1,1,2-trimethylpropyl)amino,        N-ethyl-N-(1,2,2-trimethylpropyl)amino,        N-ethyl-N-(1-ethyl-1-methylpropyl)amino,        N-ethyl-N-(1-ethyl-2-methylpropyl)amino, N-propyl-N-pentylamino,        N-butyl-N-pentylamino, N,N-dipentylamino, N-propyl-N-hexylamino,        N-butyl-N-hexylamino, N-pentyl-N-hexylamino or N,N-dihexylamino;    -   three- to six-membered heterocyclyl: monocyclic saturated or        partially unsaturated hydrocarbon having three to six ring        members as mentioned above which, in addition to carbon atoms,        contains one or two heteroatoms selected from O, S and N;        for example 2-oxiranyl, 2-oxetanyl, 3-oxetanyl, 2-aziridinyl,        3-thietanyl, 1-azetidinyl, 2-azetidinyl,        for example 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,        2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl,        3-pyrrolidinyl, 3-isoxazolidinyl, 4-isoxazolidinyl,        5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl,        5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl,        5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl,        2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl,        2-imidazolidinyl, 4-imidazolidinyl;        for example 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl,        2,4-dihydrofur-2-yl, 2,4-dihydrofur-3-yl, 2,3-dihydrothien-2-yl,        2,3-dihydrothien-3-yl, 2,4-dihydrothien-2-yl,        2,4-dihydrothien-3-yl, 4,5-dihydropyrrol-2-yl,        4,5-dihydropyrrol-3-yl, 2,5-dihydropyrrol-2-yl,        2,5-dihydropyrrol-3-yl, 4,5-dihydroisoxazol-3-yl,        2,5-dihydroisoxazol-3-yl, 2,3-dihydroisoxazol-3-yl,        4,5-dihydroisoxazol-4-yl, 2,5-dihydroisoxazol-4-yl,        2,3-dihydroisoxazol-4-yl, 4,5-dihydroisoxazol-5-yl,        2,5-dihydroisoxazol-5-yl, 2,3-dihydroisoxazol-5-yl,        4,5-dihydroisothiazol-3-yl, 2,5-dihydroisothiazol-3-yl,        2,3-dihydroisothiazol-3-yl, 4,5-dihydroisothiazol-4-yl,        2,5-dihydroisothiazol-4-yl, 2,3-dihydroisothiazol-4-yl,        4,5-dihydroisothiazol-5-yl, 2,5-dihydroisothiazol-5-yl,        2,3-dihydroisothiazol-5-yl, 2,3-dihydropyrazol-2-yl,        2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl,        2,3-dihydropyrazol-5-yl, 3,4-dihydropyrazol-3-yl,        3,4-dihydropyrazol-4-yl, 3,4-dihydropyrazol-5-yl,        4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl,        4,5-dihydropyrazol-5-yl, 2,3-dihydroimidazol-2-yl,        2,3-dihydroimidazol-3-yl, 2,3-dihydroimidazol-4-yl,        2,3-dihydroimidazol-5-yl, 4,5-dihydroimidazol-2-yl,        4,5-dihydroimidazol-4-yl, 4,5-dihydroimidazol-5-yl,        2,5-dihydroimidazol-2-yl, 2,5-dihydroimidazol-4-yl,        2,5-dihydroimidazol-5-yl, 2,3-dihydrooxazol-3-yl,        2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl,        3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl,        3,4-dihydrooxazol-5-yl, 2,3-dihydrothiazol-3-yl,        2,3-dihydrothiazol-4-yl, 2,3-dihydrothiazol-5-yl,        3,4-dihydrothiazol-3-yl, 3,4-dihydrothiazol-4-yl,        3,4-dihydrothiazol-5-yl, 3,4-dihydrothiazol-2-yl,        3,4-dihydrothiazol-3-yl, 3,4-dihydrothiazol-4-yl;        for example 2-piperidinyl, 3-piperidinyl, 4-piperidinyl,        1,3-dioxan-2-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl,        1,4-dioxan-2-yl, 1,3-dithian-2-yl, 1,3-dithian-4-yl,        1,4-dithian-2-yl, 1,3-dithian-5-yl, 2-tetrahydropyranyl,        3-tetrahydropyranyl, 4-tetrahydropyranyl,        2-tetrahydrothiopyranyl, 3-tetrahydrothiopyranyl,        4-tetrahydro-thiopyranyl, 3-hexahydropyridazinyl,        4-hexahydropyridazinyl, 2-hexahydropyrimidinyl,        4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-piperazinyl,        tetrahydro-1,3-oxazin-2-yl, tetrahydro-1,3-oxazin-6-yl,        2-morpholinyl, 3-morpholinyl;        for example 2H-pyran-2-yl, 2H-pyran-3-yl, 2H-pyran-4-yl,        2H-pyran-5-yl, 2H-pyran-6-yl, 3,6-dihydro-2H-pyran-2-yl,        3,6-dihydro-2H-pyran-3-yl, 3,6-dihydro-2H-pyran-4-yl,        3,6-dihydro-2H-pyran-5-yl, 3,6-dihydro-2H-pyran-6-yl,        3,4-dihydro-2H-pyran-3-yl, 3,4-dihydro-2H-pyran-4-yl,        3,4-dihydro-2H-pyran-6-yl, 2H-thiopyran-2-yl, 2H-thiopyran-3-yl,        2H-thiopyran-4-yl, 2H-thiopyran-5-yl, 2H-thiopyran-6-yl,        5,6-dihydro-4H-1,3-oxazin-2-yl;

The preferred embodiments of the invention mentioned herein below haveto be understood as being preferred either independently from each otheror in combination with one another.

According to a preferred embodiment of the invention preference is alsogiven to those azines of formula (I), wherein the variables, eitherindependently of one another or in combination with one another, havethe following meanings:

Preferred are the azines of formula (I), wherein

-   A is phenyl, which is substituted by two to five substituents    selected from the group consisting of halogen, CN, NO₂, C₁-C₆-alkyl,    C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy, C₁-C₆-alkylthio,    (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl, amino,    (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl,    (C₁-C₆-alkoxy)carbonyl;    -   particularly preferred phenyl, which is substituted by two to        five substituents selected from the group consisting of halogen,        CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   particularly preferred selected from halogen and CN;        -   also particularly preferred selected from the group            consisting of F, Cl, CN and CH₃;        -   especially preferred selected from the group consisting of            F, Cl and CN;    -   especially preferred phenyl, which is substituted by two to four        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   more preferred phenyl, which is substituted by two substituents        selected from the group consisting of halogen, CN, NO₂,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy, C₁-C₆-alkylthio,        (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl, amino,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   also more preferred phenyl, which is substituted by three        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   also more preferred phenyl, which is substituted by four        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN.

Also preferred are the azines of formula (I), wherein

A is

-   -   wherein    -   R^(a) and R^(e) independently of one another are halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl; and    -   R^(b), R^(c) and R^(d) independently of one another are        hydrogen, halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH,        C₁-C₆-alkoxy, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,        (C₁-C₆-alkyl)sulfonyl, amino, (C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl;    -   particularly preferred R^(a) and R^(e) independently of one        another are halogen, CN, C₁-C₆-alkyl or C₁-C₆-alkoxy; and        -   R^(b), R^(c) and R^(d) independently of one another are            hydrogen, halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl or            C₁-C₆-alkoxy;    -   especially preferred R^(a) and R^(e) independently of one        another are halogen or CN; and        -   R^(b), R^(c) and R^(d) independently of one another are            hydrogen, halogen, CN, C₁-C₆-alkyl or C₁-C₆-alkoxy;    -   more preferred R^(a) and R^(e) are halogen; and        -   R^(b), R^(c) and R^(d) independently of one another are            hydrogen, halogen or CN;    -   most preferred R^(a) and R^(e) are halogen; and        -   R^(b), R^(c) and R^(d) are hydrogen;    -   also most preferred R^(a), R^(b), R^(d) and R^(e) are halogen;        and        -   R^(c) hydrogen;    -   also most preferred R^(a), R^(b), R^(c), R^(d) and R^(e) are        halogen.

Also preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a) is halogen or CN;        -   R^(b) and R^(d) are H, halogen or CN;        -   R^(c) is H or halogen;        -   R^(e) is halogen, CN or C₁-C₆-alkyl;    -   particularly preferred R^(a) is halogen;        -   R^(b), R^(c) and R^(d) are H or halogen; and        -   R^(e) is halogen or CN;    -   especially preferred R^(a), R^(b), R^(d) and R^(e) are halogen;        and        -   R^(c) is H or halogen;    -   more preferred R^(a), R^(b), R^(d) and R^(e) are F; and        -   R^(c) is H or F.

Especially preferred are the azines of formula (I), wherein A isselected from the group consisting of (A.1.1), (A.1.2) and (A.1.3);

more preferred selected from the group consisting of (A.1.2) and(A.1.3);

-   -   wherein    -   R^(a) and R^(e) independently of one another are halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl; and    -   R^(b) and R^(d) independently of one another are halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;    -   particularly preferred R^(a) and R^(e) independently of one        another are halogen, CN, C₁-C₆-alkyl or C₁-C₆-alkoxy; and        -   R^(b) and R^(d) independently of one another are halogen,            CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl or C₁-C₆-alkoxy;    -   especially preferred R^(a) and R^(e) independently of one        another halogen or CN; and        -   R^(b) and R^(d) independently of one another are halogen,            CN, C₁-C₆-alkyl or C₁-C₆-alkoxy;    -   more preferred R^(a) and R^(e) are halogen; and        -   R^(b) and R^(d) independently of one another are halogen or            CN;    -   most preferred R^(a), R^(b), R^(d) and R^(e) are halogen.

Also especially preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a), R^(b), R^(d) and R^(e) have the meanings, in        particular the preferred meanings, as defined above.

Also especially preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a), R^(b) and R^(e) have the meanings, in particular        the preferred meanings, as defined above.

Also especially preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a) and R^(e) have the meanings, in particular the        preferred meanings, as defined above.

Also preferred are the azines of formula (I), wherein

-   A is 2-fluoro-phenyl, which is substituted by one to four    substituents selected from the group consisting of halogen, CN, NO₂,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy, C₁-C₆-alkylthio,    (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl, amino,    (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl and    (C₁-C₆-alkoxy)carbonyl;    -   particularly preferred 2-fluoro-phenyl, which is substituted by        one to four substituents selected from the group consisting of        halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   particularly preferred selected from halogen and CN;        -   also particularly preferred selected from the group            consisting of F, Cl, CN and CH₃;        -   especially preferred selected from the group consisting of            F, Cl and CN;    -   especially preferred 2-fluoro-phenyl, which is substituted by        one to three substituents selected from the group consisting of        halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH,        C₁-C₆-alkoxy, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,        (C₁-C₆-alkyl)sulfonyl, amino, (C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)-carbonyl and        (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   more preferred 2-fluoro-phenyl, which is substituted by one        substituent selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl and (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   also more preferred 2-fluoro-phenyl, which is substituted by two        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl and (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   also more preferred 2-fluoro-phenyl, which is substituted by        three substituents selected from the group consisting of        halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH,        C₁-C₆-alkoxy, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,        (C₁-C₆-alkyl)sulfonyl, amino, (C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)-carbonyl and        (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN.

Also preferred are the azines of formula (I), wherein

A is

-   -   wherein    -   R^(a) is halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH,        C₁-C₆-alkoxy, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,        (C₁-C₆-alkyl)sulfonyl, amino, (C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl; and    -   R^(b), R^(c) and R^(d) independently of one another are        hydrogen, halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH,        C₁-C₆-alkoxy, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,        (C₁-C₆-alkyl)sulfonyl, amino, (C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl;    -   particularly preferred R^(a) is halogen, CN, C₁-C₆-alkyl or        C₁-C₆-alkoxy; and        -   R^(b), R^(c) and R^(d) independently of one another are            hydrogen, halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl or            C₁-C₆-alkoxy;    -   especially preferred R^(a) is halogen or CN; and        -   R^(b), R^(c) and R^(d) independently of one another are            hydrogen, halogen, CN, C₁-C₆-alkyl or C₁-C₆-alkoxy;    -   more preferred R^(a) is halogen; and        -   R^(b), R^(c) and R^(d) independently of one another are            hydrogen, halogen or CN;    -   most preferred R^(a) is halogen; and        -   R^(b), R^(c) and R^(d) are hydrogen;    -   also most preferred R^(a), R^(b) and R^(d) are halogen; and        -   R^(c) is hydrogen;    -   also most preferred R^(a), R^(b), R^(c) and R^(d) are halogen.

Also preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a) is halogen, CN or C₁-C₆-alkyl;        -   R^(b) and R^(d) are H, halogen or CN; and        -   R^(c) is H or halogen;    -   particularly preferred R^(a) is halogen or CN; and        -   R^(b), R^(c) and R^(d) are H or halogen;    -   especially preferred R^(a), R^(b) and R^(d) are halogen; and        -   R^(c) is H or halogen;    -   Also especially preferred R^(a), R^(b) and R^(d) are halogen;        and        -   R^(c) is H, F, Br or I;    -   more preferred R^(a), R^(b) and R^(d) are F; and        -   R^(c) is F, Br or I;    -   also more preferred R^(a), R^(b) and R^(d) are F; and        -   R^(c) is H or F.

Especially preferred are the azines of formula (I), wherein A isselected from the group consisting of (A.1a.1), (A.1a.2) and (A.1a.3);

more preferred selected from the group consisting of (A.1.2) and(A.1.3);

-   -   wherein    -   R^(a) is halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH,        C₁-C₆-alkoxy, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,        (C₁-C₆-alkyl)sulfonyl, amino, (C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl; and    -   R^(b) and R^(d) independently of one another are halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;    -   particularly preferred R^(a) is halogen, CN, C₁-C₆-alkyl or        C₁-C₆-alkoxy; and        -   R^(b) and R^(d) independently of one another are halogen,            CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl or C₁-C₆-alkoxy;    -   especially preferred R^(a) is halogen or CN; and        -   R^(b) and R^(d) independently of one another are halogen,            CN, C₁-C₆-alkyl or C₁-C₆-alkoxy;    -   more preferred R^(a) is halogen; and        -   R^(b) and R^(d) independently of one another are halogen or            CN;    -   most preferred R^(a), R^(b) and R^(d) are halogen.

Also especially preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a), R^(b) and R^(d) have the meanings, in particular        the preferred meanings, as defined above.

Also especially preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a) and R^(b) have the meanings, in particular the        preferred meanings, as defined above.

Also especially preferred are the azines of formula (I), wherein

A is

-   -   wherein R^(a) has the meanings, in particular the preferred        meanings, as defined above.

Also preferred are the azines of formula (I), wherein

-   R¹ is H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,    C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or (C₁-C₆-alkyl)sulfonyl;    -   particularly preferred H, CN, C₁-C₆-alkyl,        C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or        (C₁-C₆-alkyl)sulfonyl;    -   especially preferred H, CN, CH₃, CH₂OCH₃, OCH₃, COCH₃ or SO₂CH₃;    -   more preferred hydrogen.

Also preferred are the azines of formula (I), wherein

-   R² is H, halogen, C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   particularly preferred halogen, C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   also particularly preferred H, F, Cl, CH₃ or CF₃.

Also preferred are the azines of formula (I), wherein

-   R³ and R⁴ are    -   independently of one another H, halogen, C₁-C₆-alkyl or        C₁-C₆-haloalkyl; or together with the carbon atom to which they        are attached form a moiety selected from the group consisting of        C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl and three- to six-membered        heterocyclyl,        -   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl or the            three- to six-membered heterocyclyl is unsubstituted or            substituted by one to three substituents selected from            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;    -   independently of one another particularly preferred H, halogen,        C₁-C₆-alkyl or C₁-C₆-haloalkyl; or    -   together with the carbon atom to which they are attached form a        moiety selected from the group consisting of C₃-C₆-cycloalkyl        and C₃-C₆-cycloalkenyl,        -   wherein the C₃-C₆-cycloalkyl or C₃-C₆-cycloalkenyl is            unsubstituted or substituted by one to three substituents            selected from halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;    -   independently of one another especially preferred H, halogen,        C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   independently of one another more preferred H, halogen or        C₁-C₆-alkyl.

Also preferred are the azines of formula (I), wherein

-   -   R² is H, halogen, C₁-C₆-alkyl; and    -   R³ and R⁴ are independently of one another H, halogen,        C₁-C₆-alkyl, or together with the carbon atom to which they are        attached form a C₃-C₆-cycloalkyl;    -   particularly preferred R² is H, halogen or C₁-C₆-alkyl;        -   R³ is C₁-C₆-alkyl;        -   R⁴ is H, halogen or C₁-C₆-alkyl;        -   R³ and R⁴ together with the carbon atom to which they are            attached form a C₃-C₆-cycloalkyl;    -   especially preferred R² is halogen or C₁-C₆-alkyl;        -   R³ is C₁-C₆-alkyl;        -   R⁴ is H or C₁-C₆-alkyl;    -   more preferred R² is halogen; and        -   R³ and R⁴ are C₁-C₆-alkyl.

Also preferred are the azines of formula (I), wherein

-   R⁵ is H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,    C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or (C₁-C₆-alkyl)sulfonyl;    -   particularly preferred H, CN, C₁-C₆-alkyl,        C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or        (C₁-C₆-alkyl)sulfonyl;    -   especially preferred H, CN, CH₃, CH₂OCH₃, OCH₃, COCH₃ or SO₂CH₃;    -   more preferred hydrogen.

Also preferred are the azines of formula (I), wherein

-   A is phenyl, which is substituted by two to five substituents    -   selected from the group consisting of halogen, CN, C₁-C₆-alkyl        and C₁-C₆-alkoxy;    -   particularly preferred selected from halogen and CN;    -   also particularly preferred selected from the group consisting        of F, Cl, CN and CH₃;    -   especially preferred selected from the group consisting of F, Cl        and CN;    -   particularly preferred phenyl, which is substituted by two to        four substituents selected from the group consisting of halogen,        CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   especially preferred phenyl, which is substituted by two        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   also especially preferred phenyl, which is substituted by three        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;    -   also specially preferred phenyl, which is substituted by four        substituents selected from the group consisting of halogen, CN,        NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        amino, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl;        -   particularly preferred selected from the group consisting of            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;        -   especially preferred selected from halogen and CN;        -   also especially preferred selected from the group consisting            of F, Cl, CN and CH₃;        -   more preferred selected from the group consisting of F, Cl            and CN;-   R¹ is H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,    C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or (C₁-C₆-alkyl)sulfonyl;    -   particularly preferred H, CN, C₁-C₆-alkyl,        C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or        (C₁-C₆-alkyl)sulfonyl;    -   especially preferred H, CN, CH₃, CH₂OCH₃, OCH₃, COCH₃ or SO₂CH₃;    -   more preferred hydrogen.-   R² is H, halogen, C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   particularly preferred halogen, C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   also particularly preferred H, F, CH₃ or CF₃;-   R³ and R⁴ are independently of one another H, halogen, C₁-C₆-alkyl    or C₁-C₆-haloalkyl; or    -   together with the carbon atom to which they are attached form a        moiety selected from the group consisting of C₃-C₆-cycloalkyl,        C₃-C₆-cycloalkenyl and three- to six-membered heterocyclyl,        -   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl or the            three- to six-membered heterocyclyl is unsubstituted or            substituted by one to three substituents selected from            halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;    -   independently of one another particularly preferred H, halogen,        C₁-C₆-alkyl or C₁-C₆-haloalkyl; or    -   together with the carbon atom to which they are attached form a        moiety selected from the group consisting of C₃-C₆-cycloalkyl        and C₃-C₆-cycloalkenyl,        -   wherein the C₃-C₆-cycloalkyl or C₃-C₆-cycloalkenyl is            unsubstituted or substituted by one to three substituents            selected from halogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy;    -   independently of one another especially preferred H, halogen,        C₁-C₆-alkyl or C₁-C₆-haloalkyl;    -   independently of one another more preferred H, halogen or        C₁-C₆-alkyl;        and-   R⁵ is H, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl,    C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or (C₁-C₆-alkyl)sulfonyl;    -   particularly preferred H, CN, C₁-C₆-alkyl,        C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy, (C₁-C₆-alkyl)carbonyl or        (C₁-C₆-alkyl)sulfonyl;    -   especially preferred H, CN, CH₃, CH₂OCH₃, OCH₃, COCH₃ or SO₂CH₃;    -   more preferred hydrogen.

Particular preference is given to azines of formula (I.a), whichcorrespond to azines of formula (I) wherein A is (A.1) and R¹ and R⁵ areH:

-   -   wherein the variables R^(a), R^(b), R^(c), R^(d), R^(e), R², R³        and R⁴ have the meanings, in particular the preferred meanings,        as defined above;        special preference is given to the azines of the formulae        (I.a.1) to (I.a.1406) of Table A, where the definitions of the        variables R^(a), R^(b), R^(c), R^(d), R^(e), R², R³ and R⁴ are        of particular importance for the compounds according to the        invention not only in combination with one another but in each        case also on their own:

TABLE A No. R^(a) R^(b) R^(c) R^(d) R^(e) R² R³ R⁴ I.a.1 F H H H F CH₃ HH I.a.2 Cl H H H F CH₃ H H I.a.3 Br H H H F CH₃ H H I.a.4 CN H H H F CH₃H H I.a.5 CH₃ H H H F CH₃ H H I.a.6 F H H F F CH₃ H H I.a.7 Cl H H F FCH₃ H H I.a.8 F H H Cl F CH₃ H H I.a.9 Cl H H F F CH₃ H H I.a.10 CN H HF F CH₃ H H I.a.11 F H H CN F CH₃ H H I.a.12 CN H H F F CH₃ H H I.a.13 FH F H F CH₃ H H I.a.14 Cl H F H F CH₃ H H I.a.15 CN H F H F CH₃ H HI.a.16 F F F H F CH₃ H H I.a.17 Cl F F H F CH₃ H H I.a.18 F Cl F H F CH₃H H I.a.19 Cl F F H F CH₃ H H I.a.20 CN F F H F CH₃ H H I.a.21 F CN F HF CH₃ H H I.a.22 CN F F H F CH₃ H H I.a.23 F F H F F CH₃ H H I.a.24 Cl FH F F CH₃ H H I.a.25 F Cl H F F CH₃ H H I.a.26 CN F H F F CH₃ H H I.a.27F CN H F F CH₃ H H I.a.28 F F F F F CH₃ H H I.a.29 Cl F F F F CH₃ H HI.a.30 F Cl F F F CH₃ H H I.a.31 CN F F F F CH₃ H H I.a.32 F CN F F FCH₃ H H I.a.33 H F F F F CH₃ H H I.a.34 F F Br F F CH₃ H H I.a.35 F FC≡CH F F CH₃ H H I.a.36 CF₃ Cl H H F CH₃ H H I.a.37 F F I F F CH₃ H HI.a.38 F H H H F CH₃ CH₃ H I.a.39 Cl H H H F CH₃ CH₃ H I.a.40 Br H H H FCH₃ CH₃ H I.a.41 CN H H H F CH₃ CH₃ H I.a.42 CH₃ H H H F CH₃ CH₃ HI.a.43 F H H F F CH₃ CH₃ H I.a.44 Cl H H F F CH₃ CH₃ H I.a.45 F H H Cl FCH₃ CH₃ H I.a.46 Cl H H F F CH₃ CH₃ H I.a.47 CN H H F F CH₃ CH₃ H I.a.48F H H CN F CH₃ CH₃ H I.a.49 CN H H F F CH₃ CH₃ H I.a.50 F H F H F CH₃CH₃ H I.a.51 Cl H F H F CH₃ CH₃ H I.a.52 CN H F H F CH₃ CH₃ H I.a.53 F FF H F CH₃ CH₃ H I.a.54 Cl F F H F CH₃ CH₃ H I.a.55 F Cl F H F CH₃ CH₃ HI.a.56 Cl F F H F CH₃ CH₃ H I.a.57 CN F F H F CH₃ CH₃ H I.a.58 F CN F HF CH₃ CH₃ H I.a.59 CN F F H F CH₃ CH₃ H I.a.60 F F H F F CH₃ CH₃ HI.a.61 Cl F H F F CH₃ CH₃ H I.a.62 F Cl H F F CH₃ CH₃ H I.a.63 CN F H FF CH₃ CH₃ H I.a.64 F CN H F F CH₃ CH₃ H I.a.65 F F F F F CH₃ CH₃ HI.a.66 Cl F F F F CH₃ CH₃ H I.a.67 F Cl F F F CH₃ CH₃ H I.a.68 CN F F FF CH₃ CH₃ H I.a.69 F CN F F F CH₃ CH₃ H I.a.70 H F F F F CH₃ CH₃ HI.a.71 F F Br F F CH₃ CH₃ H I.a.72 F F C≡CH F F CH₃ CH₃ H I.a.73 CF₃ ClH H F CH₃ CH₃ H I.a.74 F F I F F CH₃ CH₃ H I.a.75 F H H H F CH₃ CH₃ CH₃I.a.76 Cl H H H F CH₃ CH₃ CH₃ I.a.77 Br H H H F CH₃ CH₃ CH₃ I.a.78 CN HH H F CH₃ CH₃ CH₃ I.a.79 CH₃ H H H F CH₃ CH₃ CH₃ I.a.80 F H H F F CH₃CH₃ CH₃ I.a.81 Cl H H F F CH₃ CH₃ CH₃ I.a.82 F H H Cl F CH₃ CH₃ CH₃I.a.83 Cl H H F F CH₃ CH₃ CH₃ I.a.84 CN H H F F CH₃ CH₃ CH₃ I.a.85 F H HCN F CH₃ CH₃ CH₃ I.a.86 CN H H F F CH₃ CH₃ CH₃ I.a.87 F H F H F CH₃ CH₃CH₃ I.a.88 Cl H F H F CH₃ CH₃ CH₃ I.a.89 CN H F H F CH₃ CH₃ CH₃ I.a.90 FF F H F CH₃ CH₃ CH₃ I.a.91 Cl F F H F CH₃ CH₃ CH₃ I.a.92 F Cl F H F CH₃CH₃ CH₃ I.a.93 Cl F F H F CH₃ CH₃ CH₃ I.a.94 CN F F H F CH₃ CH₃ CH₃I.a.95 F CN F H F CH₃ CH₃ CH₃ I.a.96 CN F F H F CH₃ CH₃ CH₃ I.a.97 F F HF F CH₃ CH₃ CH₃ I.a.98 Cl F H F F CH₃ CH₃ CH₃ I.a.99 F Cl H F F CH₃ CH₃CH₃ I.a.100 CN F H F F CH₃ CH₃ CH₃ I.a.101 F CN H F F CH₃ CH₃ CH₃I.a.102 F F F F F CH₃ CH₃ CH₃ I.a.103 Cl F F F F CH₃ CH₃ CH₃ I.a.104 FCl F F F CH₃ CH₃ CH₃ I.a.105 CN F F F F CH₃ CH₃ CH₃ I.a.106 F CN F F FCH₃ CH₃ CH₃ I.a.107 H F F F F CH₃ CH₃ CH₃ I.a.108 F F Br F F CH₃ CH₃ CH₃I.a.109 F F C≡CH F F CH₃ CH₃ CH₃ I.a.110 CF₃ Cl H H F CH₃ CH₃ CH₃I.a.111 F F I F F CH₃ CH₃ CH₃ I.a.112 F H H H F F F F I.a.113 Cl H H H FF F F I.a.114 Br H H H F F F F I.a.115 CN H H H F F F F I.a.116 CH₃ H HH F F F F I.a.117 F H H F F F F F I.a.118 Cl H H F F F F F I.a.119 F H HCl F F F F I.a.120 Cl H H F F F F F I.a.121 CN H H F F F F F I.a.122 F HH CN F F F F I.a.123 CN H H F F F F F I.a.124 F H F H F F F F I.a.125 ClH F H F F F F I.a.126 CN H F H F F F F I.a.127 F F F H F F F F I.a.128Cl F F H F F F F I.a.129 F Cl F H F F F F I.a.130 Cl F F H F F F FI.a.131 CN F F H F F F F I.a.132 F CN F H F F F F I.a.133 CN F F H F F FF I.a.134 F F H F F F F F I.a.135 Cl F H F F F F F I.a.136 F Cl H F F FF F I.a.137 CN F H F F F F F I.a.138 F CN H F F F F F I.a.139 F F F F FF F F I.a.140 Cl F F F F F F F I.a.141 F Cl F F F F F F I.a.142 CN F F FF F F F I.a.143 F CN F F F F F F I.a.144 H F F F F F F F I.a.145 F F BrF F F F F I.a.146 F F C≡CH F F F F F I.a.147 CF₃ Cl H H F F F F I.a.148F F I F F F F F I.a.149 F H H H F F CF₃ F I.a.150 Cl H H H F F CF₃ FI.a.151 Br H H H F F CF₃ F I.a.152 CN H H H F F CF₃ F I.a.153 CH₃ H H HF F CF₃ F I.a.154 F H H F F F CF₃ F I.a.155 Cl H H F F F CF₃ F I.a.156 FH H Cl F F CF₃ F I.a.157 Cl H H F F F CF₃ F I.a.158 CN H H F F F CF₃ FI.a.159 F H H CN F F CF₃ F I.a.160 CN H H F F F CF₃ F I.a.161 F H F H FF CF₃ F I.a.162 Cl H F H F F CF₃ F I.a.163 CN H F H F F CF₃ F I.a.164 FF F H F F CF₃ F I.a.165 Cl F F H F F CF₃ F I.a.166 F Cl F H F F CF₃ FI.a.167 Cl F F H F F CF₃ F I.a.168 CN F F H F F CF₃ F I.a.169 F CN F H FF CF₃ F I.a.170 CN F F H F F CF₃ F I.a.171 F F H F F F CF₃ F I.a.172 ClF H F F F CF₃ F I.a.173 F Cl H F F F CF₃ F I.a.174 CN F H F F F CF₃ FI.a.175 F CN H F F F CF₃ F I.a.176 F F F F F F CF₃ F I.a.177 Cl F F F FF CF₃ F I.a.178 F Cl F F F F CF₃ F I.a.179 CN F F F F F CF₃ F I.a.180 FCN F F F F CF₃ F I.a.181 H F F F F F CF₃ F I.a.182 F F Br F F F CF₃ FI.a.183 F F C≡CH F F F CF₃ F I.a.184 CF₃ Cl H H F F CF₃ F I.a.185 F F IF F F CF₃ F I.a.186 F H H H F F CH₃ F I.a.187 Cl H H H F F CH₃ F I.a.188Br H H H F F CH₃ F I.a.189 CN H H H F F CH₃ F I.a.190 CH₃ H H H F F CH₃F I.a.191 F H H F F F CH₃ F I.a.192 Cl H H F F F CH₃ F I.a.193 F H H ClF F CH₃ F I.a.194 Cl H H F F F CH₃ F I.a.195 CN H H F F F CH₃ F I.a.196F H H CN F F CH₃ F I.a.197 CN H H F F F CH₃ F I.a.198 F H F H F F CH₃ FI.a.199 Cl H F H F F CH₃ F I.a.200 CN H F H F F CH₃ F I.a.201 F F F H FF CH₃ F I.a.202 Cl F F H F F CH₃ F I.a.203 F Cl F H F F CH₃ F I.a.204 ClF F H F F CH₃ F I.a.205 CN F F H F F CH₃ F I.a.206 F CN F H F F CH₃ FI.a.207 CN F F H F F CH₃ F I.a.208 F F H F F F CH₃ F I.a.209 Cl F H F FF CH₃ F I.a.210 F Cl H F F F CH₃ F I.a.211 CN F H F F F CH₃ F I.a.212 FCN H F F F CH₃ F I.a.213 F F F F F F CH₃ F I.a.214 Cl F F F F F CH₃ FI.a.215 F Cl F F F F CH₃ F I.a.216 CN F F F F F CH₃ F I.a.217 F CN F F FF CH₃ F I.a.218 H F F F F F CH₃ F I.a.219 F F Br F F F CH₃ F I.a.220 F FC≡CH F F F CH₃ F I.a.221 CF₃ Cl H H F F CH₃ F I.a.222 F F I F F F CH₃ FI.a.223 F H H H F F CH₃ H I.a.224 Cl H H H F F CH₃ H I.a.225 Br H H H FF CH₃ H I.a.226 CN H H H F F CH₃ H I.a.227 CH₃ H H H F F CH₃ H I.a.228 FH H F F F CH₃ H I.a.229 Cl H H F F F CH₃ H I.a.230 F H H Cl F F CH₃ HI.a.231 Cl H H F F F CH₃ H I.a.232 CN H H F F F CH₃ H I.a.233 F H H CN FF CH₃ H I.a.234 CN H H F F F CH₃ H I.a.235 F H F H F F CH₃ H I.a.236 ClH F H F F CH₃ H I.a.237 CN H F H F F CH₃ H I.a.238 F F F H F F CH₃ HI.a.239 Cl F F H F F CH₃ H I.a.240 F Cl F H F F CH₃ H I.a.241 Cl F F H FF CH₃ H I.a.242 CN F F H F F CH₃ H I.a.243 F CN F H F F CH₃ H I.a.244 CNF F H F F CH₃ H I.a.245 F F H F F F CH₃ H I.a.246 Cl F H F F F CH₃ HI.a.247 F Cl H F F F CH₃ H I.a.248 CN F H F F F CH₃ H I.a.249 F CN H F FF CH₃ H I.a.250 F F F F F F CH₃ H I.a.251 Cl F F F F F CH₃ H I.a.252 FCl F F F F CH₃ H I.a.253 CN F F F F F CH₃ H I.a.254 F CN F F F F CH₃ HI.a.255 H F F F F F CH₃ H I.a.256 F F Br F F F CH₃ H I.a.257 F F C≡CH FF F CH₃ H I.a.258 CF₃ Cl H H F F CH₃ H I.a.259 F F I F F F CH₃ H I.a.260F H H H F F CH₃ CH₃ I.a.261 Cl H H H F F CH₃ CH₃ I.a.262 Br H H H F FCH₃ CH₃ I.a.263 CN H H H F F CH₃ CH₃ I.a.264 CH₃ H H H F F CH₃ CH₃I.a.265 F H H F F F CH₃ CH₃ I.a.266 Cl H H F F F CH₃ CH₃ I.a.267 F H HCl F F CH₃ CH₃ I.a.268 Cl H H F F F CH₃ CH₃ I.a.269 CN H H F F F CH₃ CH₃I.a.270 F H H CN F F CH₃ CH₃ I.a.271 CN H H F F F CH₃ CH₃ I.a.272 F H FH F F CH₃ CH₃ I.a.273 Cl H F H F F CH₃ CH₃ I.a.274 CN H F H F F CH₃ CH₃I.a.275 F F F H F F CH₃ CH₃ I.a.276 Cl F F H F F CH₃ CH₃ I.a.277 F Cl FH F F CH₃ CH₃ I.a.278 Cl F F H F F CH₃ CH₃ I.a.279 CN F F H F F CH₃ CH₃I.a.280 F CN F H F F CH₃ CH₃ I.a.281 CN F F H F F CH₃ CH₃ I.a.282 F F HF F F CH₃ CH₃ I.a.283 Cl F H F F F CH₃ CH₃ I.a.284 F Cl H F F F CH₃ CH₃I.a.285 CN F H F F F CH₃ CH₃ I.a.286 F CN H F F F CH₃ CH₃ I.a.287 F F FF F F CH₃ CH₃ I.a.288 Cl F F F F F CH₃ CH₃ I.a.289 F Cl F F F F CH₃ CH₃I.a.290 CN F F F F F CH₃ CH₃ I.a.291 F CN F F F F CH₃ CH₃ I.a.292 H F FF F F CH₃ CH₃ I.a.293 F F Br F F F CH₃ CH₃ I.a.294 F F C≡CH F F F CH₃CH₃ I.a.295 CF₃ Cl H H F F CH₃ CH₃ I.a.296 F F I F F F CH₃ CH₃ I.a.297 FH H H F Cl CH₃ CH₃ I.a.298 Cl H H H F Cl CH₃ CH₃ I.a.299 Br H H H F ClCH₃ CH₃ I.a.300 CN H H H F Cl CH₃ CH₃ I.a.301 CH₃ H H H F Cl CH₃ CH₃I.a.302 F H H F F Cl CH₃ CH₃ I.a.303 Cl H H F F Cl CH₃ CH₃ I.a.304 F H HCl F Cl CH₃ CH₃ I.a.305 Cl H H F F Cl CH₃ CH₃ I.a.306 CN H H F F Cl CH₃CH₃ I.a.307 F H H CN F Cl CH₃ CH₃ I.a.308 CN H H F F Cl CH₃ CH₃ I.a.309F H F H F Cl CH₃ CH₃ I.a.310 Cl H F H F Cl CH₃ CH₃ I.a.311 CN H F H F ClCH₃ CH₃ I.a.312 F F F H F Cl CH₃ CH₃ I.a.313 Cl F F H F Cl CH₃ CH₃I.a.314 F Cl F H F Cl CH₃ CH₃ I.a.315 Cl F F H F Cl CH₃ CH₃ I.a.316 CN FF H F Cl CH₃ CH₃ I.a.317 F CN F H F Cl CH₃ CH₃ I.a.318 CN F F H F Cl CH₃CH₃ I.a.319 F F H F F Cl CH₃ CH₃ I.a.320 Cl F H F F Cl CH₃ CH₃ I.a.321 FCl H F F Cl CH₃ CH₃ I.a.322 CN F H F F Cl CH₃ CH₃ I.a.323 F CN H F F ClCH₃ CH₃ I.a.324 F F F F F Cl CH₃ CH₃ I.a.325 Cl F F F F Cl CH₃ CH₃I.a.326 F Cl F F F Cl CH₃ CH₃ I.a.327 CN F F F F Cl CH₃ CH₃ I.a.328 F CNF F F Cl CH₃ CH₃ I.a.329 H F F F F Cl CH₃ CH₃ I.a.330 F F Br F F Cl CH₃CH₃ I.a.331 F F C≡CH F F Cl CH₃ CH₃ I.a.332 CF₃ Cl H H F Cl CH₃ CH₃I.a.333 F F I F F Cl CH₃ CH₃ I.a.334 F H H H F F C₂H₅ CH₃ I.a.335 Cl H HH F F C₂H₅ CH₃ I.a.336 Br H H H F F C₂H₅ CH₃ I.a.337 CN H H H F F C₂H₅CH₃ I.a.338 CH₃ H H H F F C₂H₅ CH₃ I.a.339 F H H F F F C₂H₅ CH₃ I.a.340Cl H H F F F C₂H₅ CH₃ I.a.341 F H H Cl F F C₂H₅ CH₃ I.a.342 Cl H H F F FC₂H₅ CH₃ I.a.343 CN H H F F F C₂H₅ CH₃ I.a.344 F H H CN F F C₂H₅ CH₃I.a.345 CN H H F F F C₂H₅ CH₃ I.a.346 F H F H F F C₂H₅ CH₃ I.a.347 Cl HF H F F C₂H₅ CH₃ I.a.348 CN H F H F F C₂H₅ CH₃ I.a.349 F F F H F F C₂H₅CH₃ I.a.350 Cl F F H F F C₂H₅ CH₃ I.a.351 F Cl F H F F C₂H₅ CH₃ I.a.352Cl F F H F F C₂H₅ CH₃ I.a.353 CN F F H F F C₂H₅ CH₃ I.a.354 F CN F H F FC₂H₅ CH₃ I.a.355 CN F F H F F C₂H₅ CH₃ I.a.356 F F H F F F C₂H₅ CH₃I.a.357 Cl F H F F F C₂H₅ CH₃ I.a.358 F Cl H F F F C₂H₅ CH₃ I.a.359 CN FH F F F C₂H₅ CH₃ I.a.360 F CN H F F F C₂H₅ CH₃ I.a.361 F F F F F F C₂H₅CH₃ I.a.362 Cl F F F F F C₂H₅ CH₃ I.a.363 F Cl F F F F C₂H₅ CH₃ I.a.364CN F F F F F C₂H₅ CH₃ I.a.365 F CN F F F F C₂H₅ CH₃ I.a.366 H F F F F FC₂H₅ CH₃ I.a.367 F F Br F F F C₂H₅ CH₃ I.a.368 F F C≡CH F F F C₂H₅ CH₃I.a.369 CF₃ Cl H H F F C₂H₅ CH₃ I.a.370 F F I F F F C₂H₅ CH₃ I.a.371 F HH H F F C₂H₅ C₂H₅ I.a.372 Cl H H H F F C₂H₅ C₂H₅ I.a.373 Br H H H F FC₂H₅ C₂H₅ I.a.374 CN H H H F F C₂H₅ C₂H₅ I.a.375 CH₃ H H H F F C₂H₅ C₂H₅I.a.376 F H H F F F C₂H₅ C₂H₅ I.a.377 Cl H H F F F C₂H₅ C₂H₅ I.a.378 F HH Cl F F C₂H₅ C₂H₅ I.a.379 Cl H H F F F C₂H₅ C₂H₅ I.a.380 CN H H F F FC₂H₅ C₂H₅ I.a.381 F H H CN F F C₂H₅ C₂H₅ I.a.382 CN H H F F F C₂H₅ C₂H₅I.a.383 F H F H F F C₂H₅ C₂H₅ I.a.384 Cl H F H F F C₂H₅ C₂H₅ I.a.385 CNH F H F F C₂H₅ C₂H₅ I.a.386 F F F H F F C₂H₅ C₂H₅ I.a.387 Cl F F H F FC₂H₅ C₂H₅ I.a.388 F Cl F H F F C₂H₅ C₂H₅ I.a.389 Cl F F H F F C₂H₅ C₂H₅I.a.390 CN F F H F F C₂H₅ C₂H₅ I.a.391 F CN F H F F C₂H₅ C₂H₅ I.a.392 CNF F H F F C₂H₅ C₂H₅ I.a.393 F F H F F F C₂H₅ C₂H₅ I.a.394 Cl F H F F FC₂H₅ C₂H₅ I.a.395 F Cl H F F F C₂H₅ C₂H₅ I.a.396 CN F H F F F C₂H₅ C₂H₅I.a.397 F CN H F F F C₂H₅ C₂H₅ I.a.398 F F F F F F C₂H₅ C₂H₅ I.a.399 ClF F F F F C₂H₅ C₂H₅ I.a.400 F Cl F F F F C₂H₅ C₂H₅ I.a.401 CN F F F F FC₂H₅ C₂H₅ I.a.402 F CN F F F F C₂H₅ C₂H₅ I.a.403 H F F F F F C₂H₅ C₂H₅I.a.404 F F Br F F F C₂H₅ C₂H₅ I.a.405 F F C≡CH F F F C₂H₅ C₂H₅ I.a.406CF₃ Cl H H F F C₂H₅ C₂H₅ I.a.407 F F I F F F C₂H₅ C₂H₅ I.a.408 F H H H FH —(CH₂)₂— I.a.409 Cl H H H F H —(CH₂)₂— I.a.410 Br H H H F H —(CH₂)₂—I.a.411 CN H H H F H —(CH₂)₂— I.a.412 CH₃ H H H F H —(CH₂)₂— I.a.413 F HH F F H —(CH₂)₂— I.a.414 Cl H H F F H —(CH₂)₂— I.a.415 F H H Cl F H—(CH₂)₂— I.a.416 Cl H H F F H —(CH₂)₂— I.a.417 CN H H F F H —(CH₂)₂—I.a.418 F H H CN F H —(CH₂)₂— I.a.419 CN H H F F H —(CH₂)₂— I.a.420 F HF H F H —(CH₂)₂— I.a.421 Cl H F H F H —(CH₂)₂— I.a.422 CN H F H F H—(CH₂)₂— I.a.423 F F F H F H —(CH₂)₂— I.a.424 Cl F F H F H —(CH₂)₂—I.a.425 F Cl F H F H —(CH₂)₂— I.a.426 Cl F F H F H —(CH₂)₂— I.a.427 CN FF H F H —(CH₂)₂— I.a.428 F CN F H F H —(CH₂)₂— I.a.429 CN F F H F H—(CH₂)₂— I.a.430 F F H F F H —(CH₂)₂— I.a.431 Cl F H F F H —(CH₂)₂—I.a.432 F Cl H F F H —(CH₂)₂— I.a.433 CN F H F F H —(CH₂)₂— I.a.434 F CNH F F H —(CH₂)₂— I.a.435 F F F F F H —(CH₂)₂— I.a.436 Cl F F F F H—(CH₂)₂— I.a.437 F Cl F F F H —(CH₂)₂— I.a.438 CN F F F F H —(CH₂)₂—I.a.439 F CN F F F H —(CH₂)₂— I.a.440 H F F F F H —(CH₂)₂— I.a.441 F FBr F F H —(CH₂)₂— I.a.442 F F C≡CH F F H —(CH₂)₂— I.a.443 CF₃ Cl H H F H—(CH₂)₂— I.a.444 F F I F F H —(CH₂)₂— I.a.445 F H H H F H —(CH₂)₃—I.a.446 Cl H H H F H —(CH₂)₃— I.a.447 Br H H H F H —(CH₂)₃— I.a.448 CN HH H F H —(CH₂)₃— I.a.449 CH₃ H H H F H —(CH₂)₃— I.a.450 F H H F F H—(CH₂)₃— I.a.451 Cl H H F F H —(CH₂)₃— I.a.452 F H H Cl F H —(CH₂)₃—I.a.453 Cl H H F F H —(CH₂)₃— I.a.454 CN H H F F H —(CH₂)₃— I.a.455 F HH CN F H —(CH₂)₃— I.a.456 CN H H F F H —(CH₂)₃— I.a.457 F H F H F H—(CH₂)₃— I.a.458 Cl H F H F H —(CH₂)₃— I.a.459 CN H F H F H —(CH₂)₃—I.a.460 F F F H F H —(CH₂)₃— I.a.461 Cl F F H F H —(CH₂)₃— I.a.462 F ClF H F H —(CH₂)₃— I.a.463 Cl F F H F H —(CH₂)₃— I.a.464 CN F F H F H—(CH₂)₃— I.a.465 F CN F H F H —(CH₂)₃— I.a.466 CN F F H F H —(CH₂)₃—I.a.467 F F H F F H —(CH₂)₃— I.a.468 Cl F H F F H —(CH₂)₃— I.a.469 F ClH F F H —(CH₂)₃— I.a.470 CN F H F F H —(CH₂)₃— I.a.471 F CN H F F H—(CH₂)₃— I.a.472 F F F F F H —(CH₂)₃— I.a.473 Cl F F F F H —(CH₂)₃—I.a.474 F Cl F F F H —(CH₂)₃— I.a.475 CN F F F F H —(CH₂)₃— I.a.476 F CNF F F H —(CH₂)₃— I.a.477 H F F F F H —(CH₂)₃— I.a.478 F F Br F F H—(CH₂)₃— I.a.479 F F C≡CH F F H —(CH₂)₃— I.a.480 CF₃ Cl H H F H —(CH₂)₃—I.a.481 F F I F F H —(CH₂)₃— I.a.482 F H H H F H —(CH₂)₄— I.a.483 Cl H HH F H —(CH₂)₄— I.a.484 Br H H H F H —(CH₂)₄— I.a.485 CN H H H F H—(CH₂)₄— I.a.486 CH₃ H H H F H —(CH₂)₄— I.a.487 F H H F F H —(CH₂)₄—I.a.488 Cl H H F F H —(CH₂)₄— I.a.489 F H H Cl F H —(CH₂)₄— I.a.490 Cl HH F F H —(CH₂)₄— I.a.491 CN H H F F H —(CH₂)₄— I.a.492 F H H CN F H—(CH₂)₄— I.a.493 CN H H F F H —(CH₂)₄— I.a.494 F H F H F H —(CH₂)₄—I.a.495 Cl H F H F H —(CH₂)₄— I.a.496 CN H F H F H —(CH₂)₄— I.a.497 F FF H F H —(CH₂)₄— I.a.498 Cl F F H F H —(CH₂)₄— I.a.499 F Cl F H F H—(CH₂)₄— I.a.500 Cl F F H F H —(CH₂)₄— I.a.501 CN F F H F H —(CH₂)₄—I.a.502 F CN F H F H —(CH₂)₄— I.a.503 CN F F H F H —(CH₂)₄— I.a.504 F FH F F H —(CH₂)₄— I.a.505 Cl F H F F H —(CH₂)₄— I.a.506 F Cl H F F H—(CH₂)₄— I.a.507 CN F H F F H —(CH₂)₄— I.a.508 F CN H F F H —(CH₂)₄—I.a.509 F F F F F H —(CH₂)₄— I.a.510 Cl F F F F H —(CH₂)₄— I.a.511 F ClF F F H —(CH₂)₄— I.a.512 CN F F F F H —(CH₂)₄— I.a.513 F CN F F F H—(CH₂)₄— I.a.514 H F F F F H —(CH₂)₄— I.a.515 F F Br F F H —(CH₂)₄—I.a.516 F F C≡CH F F H —(CH₂)₄— I.a.517 CF₃ Cl H H F H —(CH₂)₄— I.a.518F F I F F H —(CH₂)₄— I.a.519 F H H H F H —(CH₂)₅— I.a.520 Cl H H H F H—(CH₂)₅— I.a.521 Br H H H F H —(CH₂)₅— I.a.522 CN H H H F H —(CH₂)₅—I.a.523 CH₃ H H H F H —(CH₂)₅— I.a.524 F H H F F H —(CH₂)₅— I.a.525 Cl HH F F H —(CH₂)₅— I.a.526 F H H Cl F H —(CH₂)₅— I.a.527 Cl H H F F H—(CH₂)₅— I.a.528 CN H H F F H —(CH₂)₅— I.a.529 F H H CN F H —(CH₂)₅—I.a.530 CN H H F F H —(CH₂)₅— I.a.531 F H F H F H —(CH₂)₅— I.a.532 Cl HF H F H —(CH₂)₅— I.a.533 CN H F H F H —(CH₂)₅— I.a.534 F F F H F H—(CH₂)₅— I.a.535 Cl F F H F H —(CH₂)₅— I.a.536 F Cl F H F H —(CH₂)₅—I.a.537 Cl F F H F H —(CH₂)₅— I.a.538 CN F F H F H —(CH₂)₅— I.a.539 F CNF H F H —(CH₂)₅— I.a.540 CN F F H F H —(CH₂)₅— I.a.541 F F H F F H—(CH₂)₅— I.a.542 Cl F H F F H —(CH₂)₅— I.a.543 F Cl H F F H —(CH₂)₅—I.a.544 CN F H F F H —(CH₂)₅— I.a.545 F CN H F F H —(CH₂)₅— I.a.546 F FF F F H —(CH₂)₅— I.a.547 Cl F F F F H —(CH₂)₅— I.a.548 F Cl F F F H—(CH₂)₅— I.a.549 CN F F F F H —(CH₂)₅— I.a.550 F CN F F F H —(CH₂)₅—I.a.551 H F F F F H —(CH₂)₅— I.a.552 F F Br F F H —(CH₂)₅— I.a.553 F FC≡CH F F H —(CH₂)₅— I.a.554 CF₃ Cl H H F H —(CH₂)₅— I.a.555 F F I F F H—(CH₂)₅— I.a.556 F H H H F CH₃ —(CH₂)₂— I.a.557 Cl H H H F CH₃ —(CH₂)₂—I.a.558 Br H H H F CH₃ —(CH₂)₂— I.a.559 CN H H H F CH₃ —(CH₂)₂— I.a.560CH₃ H H H F CH₃ —(CH₂)₂— I.a.561 F H H F F CH₃ —(CH₂)₂— I.a.562 Cl H H FF CH₃ —(CH₂)₂— I.a.563 F H H Cl F CH₃ —(CH₂)₂— I.a.564 Cl H H F F CH₃—(CH₂)₂— I.a.565 CN H H F F CH₃ —(CH₂)₂— I.a.566 F H H CN F CH₃ —(CH₂)₂—I.a.567 CN H H F F CH₃ —(CH₂)₂— I.a.568 F H F H F CH₃ —(CH₂)₂— I.a.569Cl H F H F CH₃ —(CH₂)₂— I.a.570 CN H F H F CH₃ —(CH₂)₂— I.a.571 F F F HF CH₃ —(CH₂)₂— I.a.572 Cl F F H F CH₃ —(CH₂)₂— I.a.573 F Cl F H F CH₃—(CH₂)₂— I.a.574 Cl F F H F CH₃ —(CH₂)₂— I.a.575 CN F F H F CH₃ —(CH₂)₂—I.a.576 F CN F H F CH₃ —(CH₂)₂— I.a.577 CN F F H F CH₃ —(CH₂)₂— I.a.578F F H F F CH₃ —(CH₂)₂— I.a.579 Cl F H F F CH₃ —(CH₂)₂— I.a.580 F Cl H FF CH₃ —(CH₂)₂— I.a.581 CN F H F F CH₃ —(CH₂)₂— I.a.582 F CN H F F CH₃—(CH₂)₂— I.a.583 F F F F F CH₃ —(CH₂)₂— I.a.584 Cl F F F F CH₃ —(CH₂)₂—I.a.585 F Cl F F F CH₃ —(CH₂)₂— I.a.586 CN F F F F CH₃ —(CH₂)₂— I.a.587F CN F F F CH₃ —(CH₂)₂— I.a.588 H F F F F CH₃ —(CH₂)₂— I.a.589 F F Br FF CH₃ —(CH₂)₂— I.a.590 F F C≡CH F F CH₃ —(CH₂)₂— I.a.591 CF₃ Cl H H FCH₃ —(CH₂)₂— I.a.592 F F I F F CH₃ —(CH₂)₂— I.a.593 F H H H F CH₃—(CH₂)₃— I.a.594 Cl H H H F CH₃ —(CH₂)₃— I.a.595 Br H H H F CH₃ —(CH₂)₃—I.a.596 CN H H H F CH₃ —(CH₂)₃— I.a.597 CH₃ H H H F CH₃ —(CH₂)₃— I.a.598F H H F F CH₃ —(CH₂)₃— I.a.599 Cl H H F F CH₃ —(CH₂)₃— I.a.600 F H H ClF CH₃ —(CH₂)₃— I.a.601 Cl H H F F CH₃ —(CH₂)₃— I.a.602 CN H H F F CH₃—(CH₂)₃— I.a.603 F H H CN F CH₃ —(CH₂)₃— I.a.604 CN H H F F CH₃ —(CH₂)₃—I.a.605 F H F H F CH₃ —(CH₂)₃— I.a.606 Cl H F H F CH₃ —(CH₂)₃— I.a.607CN H F H F CH₃ —(CH₂)₃— I.a.608 F F F H F CH₃ —(CH₂)₃— I.a.609 Cl F F HF CH₃ —(CH₂)₃— I.a.610 F Cl F H F CH₃ —(CH₂)₃— I.a.611 Cl F F H F CH₃—(CH₂)₃— I.a.612 CN F F H F CH₃ —(CH₂)₃— I.a.613 F CN F H F CH₃ —(CH₂)₃—I.a.614 CN F F H F CH₃ —(CH₂)₃— I.a.615 F F H F F CH₃ —(CH₂)₃— I.a.616Cl F H F F CH₃ —(CH₂)₃— I.a.617 F Cl H F F CH₃ —(CH₂)₃— I.a.618 CN F H FF CH₃ —(CH₂)₃— I.a.619 F CN H F F CH₃ —(CH₂)₃— I.a.620 F F F F F CH₃—(CH₂)₃— I.a.621 Cl F F F F CH₃ —(CH₂)₃— I.a.622 F Cl F F F CH₃ —(CH₂)₃—I.a.623 CN F F F F CH₃ —(CH₂)₃— I.a.624 F CN F F F CH₃ —(CH₂)₃— I.a.625H F F F F CH₃ —(CH₂)₃— I.a.626 F F Br F F CH₃ —(CH₂)₃— I.a.627 F F C≡CHF F CH₃ —(CH₂)₃— I.a.628 CF₃ Cl H H F CH₃ —(CH₂)₃— I.a.629 F F I F F CH₃—(CH₂)₃— I.a.630 F H H H F CH₃ —(CH₂)₄— I.a.631 Cl H H H F CH₃ —(CH₂)₄—I.a.632 Br H H H F CH₃ —(CH₂)₄— I.a.633 CN H H H F CH₃ —(CH₂)₄— I.a.634CH₃ H H H F CH₃ —(CH₂)₄— I.a.635 F H H F F CH₃ —(CH₂)₄— I.a.636 Cl H H FF CH₃ —(CH₂)₄— I.a.637 F H H Cl F CH₃ —(CH₂)₄— I.a.638 Cl H H F F CH₃—(CH₂)₄— I.a.639 CN H H F F CH₃ —(CH₂)₄— I.a.640 F H H CN F CH₃ —(CH₂)₄—I.a.641 CN H H F F CH₃ —(CH₂)₄— I.a.642 F H F H F CH₃ —(CH₂)₄— I.a.643Cl H F H F CH₃ —(CH₂)₄— I.a.644 CN H F H F CH₃ —(CH₂)₄— I.a.645 F F F HF CH₃ —(CH₂)₄— I.a.646 Cl F F H F CH₃ —(CH₂)₄— I.a.647 F Cl F H F CH₃—(CH₂)₄— I.a.648 Cl F F H F CH₃ —(CH₂)₄— I.a.649 CN F F H F CH₃ —(CH₂)₄—I.a.650 F CN F H F CH₃ —(CH₂)₄— I.a.651 CN F F H F CH₃ —(CH₂)₄— I.a.652F F H F F CH₃ —(CH₂)₄— I.a.653 Cl F H F F CH₃ —(CH₂)₄— I.a.654 F Cl H FF CH₃ —(CH₂)₄— I.a.655 CN F H F F CH₃ —(CH₂)₄— I.a.656 F CN H F F CH₃—(CH₂)₄— I.a.657 F F F F F CH₃ —(CH₂)₄— I.a.658 Cl F F F F CH₃ —(CH₂)₄—I.a.659 F Cl F F F CH₃ —(CH₂)₄— I.a.660 CN F F F F CH₃ —(CH₂)₄— I.a.661F CN F F F CH₃ —(CH₂)₄— I.a.662 H F F F F CH₃ —(CH₂)₄— I.a.663 F F Br FF CH₃ —(CH₂)₄— I.a.664 F F C≡CH F F CH₃ —(CH₂)₄— I.a.665 CF₃ Cl H H FCH₃ —(CH₂)₄— I.a.666 F F I F F CH₃ —(CH₂)₄— I.a.667 F H H H F CH₃—(CH₂)₅— I.a.668 Cl H H H F CH₃ —(CH₂)₅— I.a.669 Br H H H F CH₃ —(CH₂)₅—I.a.670 CN H H H F CH₃ —(CH₂)₅— I.a.671 CH₃ H H H F CH₃ —(CH₂)₅— I.a.672F H H F F CH₃ —(CH₂)₅— I.a.673 Cl H H F F CH₃ —(CH₂)₅— I.a.674 F H H ClF CH₃ —(CH₂)₅— I.a.675 Cl H H F F CH₃ —(CH₂)₅— I.a.676 CN H H F F CH₃—(CH₂)₅— I.a.677 F H H CN F CH₃ —(CH₂)₅— I.a.678 CN H H F F CH₃ —(CH₂)₅—I.a.679 F H F H F CH₃ —(CH₂)₅— I.a.680 Cl H F H F CH₃ —(CH₂)₅— I.a.681CN H F H F CH₃ —(CH₂)₅— I.a.682 F F F H F CH₃ —(CH₂)₅— I.a.683 Cl F F HF CH₃ —(CH₂)₅— I.a.684 F Cl F H F CH₃ —(CH₂)₅— I.a.685 Cl F F H F CH₃—(CH₂)₅— I.a.686 CN F F H F CH₃ —(CH₂)₅— I.a.687 F CN F H F CH₃ —(CH₂)₅—I.a.688 CN F F H F CH₃ —(CH₂)₅— I.a.689 F F H F F CH₃ —(CH₂)₅— I.a.690Cl F H F F CH₃ —(CH₂)₅— I.a.691 F Cl H F F CH₃ —(CH₂)₅— I.a.692 CN F H FF CH₃ —(CH₂)₅— I.a.693 F CN H F F CH₃ —(CH₂)₅— I.a.694 F F F F F CH₃—(CH₂)₅— I.a.695 Cl F F F F CH₃ —(CH₂)₅— I.a.696 F Cl F F F CH₃ —(CH₂)₅—I.a.697 CN F F F F CH₃ —(CH₂)₅— I.a.698 F CN F F F CH₃ —(CH₂)₅— I.a.699H F F F F CH₃ —(CH₂)₅— I.a.700 F F Br F F CH₃ —(CH₂)₅— I.a.701 F F C≡CHF F CH₃ —(CH₂)₅— I.a.702 CF₃ Cl H H F CH₃ —(CH₂)₅— I.a.703 F F I F F CH₃—(CH₂)₅— I.a.704 F H H H F F —(CH₂)₂— I.a.705 Cl H H H F F —(CH₂)₂—I.a.706 Br H H H F F —(CH₂)₂— I.a.707 CN H H H F F —(CH₂)₂— I.a.708 CH₃H H H F F —(CH₂)₂— I.a.709 F H H F F F —(CH₂)₂— I.a.710 Cl H H F F F—(CH₂)₂— I.a.711 F H H Cl F F —(CH₂)₂— I.a.712 Cl H H F F F —(CH₂)₂—I.a.713 CN H H F F F —(CH₂)₂— I.a.714 F H H CN F F —(CH₂)₂— I.a.715 CN HH F F F —(CH₂)₂— I.a.716 F H F H F F —(CH₂)₂— I.a.717 Cl H F H F F—(CH₂)₂— I.a.718 CN H F H F F —(CH₂)₂— I.a.719 F F F H F F —(CH₂)₂—I.a.720 Cl F F H F F —(CH₂)₂— I.a.721 F Cl F H F F —(CH₂)₂— I.a.722 Cl FF H F F —(CH₂)₂— I.a.723 CN F F H F F —(CH₂)₂— I.a.724 F CN F H F F—(CH₂)₂— I.a.725 CN F F H F F —(CH₂)₂— I.a.726 F F H F F F —(CH₂)₂—I.a.727 Cl F H F F F —(CH₂)₂— I.a.728 F Cl H F F F —(CH₂)₂— I.a.729 CN FH F F F —(CH₂)₂— I.a.730 F CN H F F F —(CH₂)₂— I.a.731 F F F F F F—(CH₂)₂— I.a.732 Cl F F F F F —(CH₂)₂— I.a.733 F Cl F F F F —(CH₂)₂—I.a.734 CN F F F F F —(CH₂)₂— I.a.735 F CN F F F F —(CH₂)₂— I.a.736 H FF F F F —(CH₂)₂— I.a.737 F F Br F F F —(CH₂)₂— I.a.738 F F C≡CH F F F—(CH₂)₂— I.a.739 CF₃ Cl H H F F —(CH₂)₂— I.a.740 F F I F F F —(CH₂)₂—I.a.741 F H H H F F —(CH₂)₃— I.a.742 Cl H H H F F —(CH₂)₃— I.a.743 Br HH H F F —(CH₂)₃— I.a.744 CN H H H F F —(CH₂)₃— I.a.745 CH₃ H H H F F—(CH₂)₃— I.a.746 F H H F F F —(CH₂)₃— I.a.747 Cl H H F F F —(CH₂)₃—I.a.748 F H H Cl F F —(CH₂)₃— I.a.749 Cl H H F F F —(CH₂)₃— I.a.750 CN HH F F F —(CH₂)₃— I.a.751 F H H CN F F —(CH₂)₃— I.a.752 CN H H F F F—(CH₂)₃— I.a.753 F H F H F F —(CH₂)₃— I.a.754 Cl H F H F F —(CH₂)₃—I.a.755 CN H F H F F —(CH₂)₃— I.a.756 F F F H F F —(CH₂)₃— I.a.757 Cl FF H F F —(CH₂)₃— I.a.758 F Cl F H F F —(CH₂)₃— I.a.759 Cl F F H F F—(CH₂)₃— I.a.760 CN F F H F F —(CH₂)₃— I.a.761 F CN F H F F —(CH₂)₃—I.a.762 CN F F H F F —(CH₂)₃— I.a.763 F F H F F F —(CH₂)₃— I.a.764 Cl FH F F F —(CH₂)₃— I.a.765 F Cl H F F F —(CH₂)₃— I.a.766 CN F H F F F—(CH₂)₃— I.a.767 F CN H F F F —(CH₂)₃— I.a.768 F F F F F F —(CH₂)₃—I.a.769 Cl F F F F F —(CH₂)₃— I.a.770 F Cl F F F F —(CH₂)₃— I.a.771 CN FF F F F —(CH₂)₃— I.a.772 F CN F F F F —(CH₂)₃— I.a.773 H F F F F F—(CH₂)₃— I.a.774 F F Br F F F —(CH₂)₃— I.a.775 F F C≡CH F F F —(CH₂)₃—I.a.776 CF₃ Cl H H F F —(CH₂)₃— I.a.777 F F I F F F —(CH₂)₃— I.a.778 F HH H F F —(CH₂)₄— I.a.779 Cl H H H F F —(CH₂)₄— I.a.780 Br H H H F F—(CH₂)₄— I.a.781 CN H H H F F —(CH₂)₄— I.a.782 CH₃ H H H F F —(CH₂)₄—I.a.783 F H H F F F —(CH₂)₄— I.a.784 Cl H H F F F —(CH₂)₄— I.a.785 F H HCl F F —(CH₂)₄— I.a.786 Cl H H F F F —(CH₂)₄— I.a.787 CN H H F F F—(CH₂)₄— I.a.788 F H H CN F F —(CH₂)₄— I.a.789 CN H H F F F —(CH₂)₄—I.a.790 F H F H F F —(CH₂)₄— I.a.791 Cl H F H F F —(CH₂)₄— I.a.792 CN HF H F F —(CH₂)₄— I.a.793 F F F H F F —(CH₂)₄— I.a.794 Cl F F H F F—(CH₂)₄— I.a.795 F Cl F H F F —(CH₂)₄— I.a.796 Cl F F H F F —(CH₂)₄—I.a.797 CN F F H F F —(CH₂)₄— I.a.798 F CN F H F F —(CH₂)₄— I.a.799 CN FF H F F —(CH₂)₄— I.a.800 F F H F F F —(CH₂)₄— I.a.801 Cl F H F F F—(CH₂)₄— I.a.802 F Cl H F F F —(CH₂)₄— I.a.803 CN F H F F F —(CH₂)₄—I.a.804 F CN H F F F —(CH₂)₄— I.a.805 F F F F F F —(CH₂)₄— I.a.806 Cl FF F F F —(CH₂)₄— I.a.807 F Cl F F F F —(CH₂)₄— I.a.808 CN F F F F F—(CH₂)₄— I.a.809 F CN F F F F —(CH₂)₄— I.a.810 H F F F F F —(CH₂)₄—I.a.811 F F Br F F F —(CH₂)₄— I.a.812 F F C≡CH F F F —(CH₂)₄— I.a.813CF₃ Cl H H F F —(CH₂)₄— I.a.814 F F I F F F —(CH₂)₄— I.a.815 F H H H F F—(CH₂)₅— I.a.816 Cl H H H F F —(CH₂)₅— I.a.817 Br H H H F F —(CH₂)₅—I.a.818 CN H H H F F —(CH₂)₅— I.a.819 CH₃ H H H F F —(CH₂)₅— I.a.820 F HH F F F —(CH₂)₅— I.a.821 Cl H H F F F —(CH₂)₅— I.a.822 F H H Cl F F—(CH₂)₅— I.a.823 Cl H H F F F —(CH₂)₅— I.a.824 CN H H F F F —(CH₂)₅—I.a.825 F H H CN F F —(CH₂)₅— I.a.826 CN H H F F F —(CH₂)₅— I.a.827 F HF H F F —(CH₂)₅— I.a.828 Cl H F H F F —(CH₂)₅— I.a.829 CN H F H F F—(CH₂)₅— I.a.830 F F F H F F —(CH₂)₅— I.a.831 Cl F F H F F —(CH₂)₅—I.a.832 F Cl F H F F —(CH₂)₅— I.a.833 Cl F F H F F —(CH₂)₅— I.a.834 CN FF H F F —(CH₂)₅— I.a.835 F CN F H F F —(CH₂)₅— I.a.836 CN F F H F F—(CH₂)₅— I.a.837 F F H F F F —(CH₂)₅— I.a.838 Cl F H F F F —(CH₂)₅—I.a.839 F Cl H F F F —(CH₂)₅— I.a.840 CN F H F F F —(CH₂)₅— I.a.841 F CNH F F F —(CH₂)₅— I.a.842 F F F F F F —(CH₂)₅— I.a.843 Cl F F F F F—(CH₂)₅— I.a.844 F Cl F F F F —(CH₂)₅— I.a.845 CN F F F F F —(CH₂)₅—I.a.846 F CN F F F F —(CH₂)₅— I.a.847 H F F F F F —(CH₂)₅— I.a.848 F FBr F F F —(CH₂)₅— I.a.849 F F C≡CH F F F —(CH₂)₅— I.a.850 CF₃ Cl H H F F—(CH₂)₅— I.a.851 F F I F F F —(CH₂)₅— I.a.852 F H H H F Cl —(CH₂)₂—I.a.853 Cl H H H F Cl —(CH₂)₂— I.a.854 Br H H H F Cl —(CH₂)₂— I.a.855 CNH H H F Cl —(CH₂)₂— I.a.856 CH₃ H H H F Cl —(CH₂)₂— I.a.857 F H H F F Cl—(CH₂)₂— I.a.858 Cl H H F F Cl —(CH₂)₂— I.a.859 F H H Cl F Cl —(CH₂)₂—I.a.860 Cl H H F F Cl —(CH₂)₂— I.a.861 CN H H F F Cl —(CH₂)₂— I.a.862 FH H CN F Cl —(CH₂)₂— I.a.863 CN H H F F Cl —(CH₂)₂— I.a.864 F H F H F Cl—(CH₂)₂— I.a.865 Cl H F H F Cl —(CH₂)₂— I.a.866 CN H F H F Cl —(CH₂)₂—I.a.867 F F F H F Cl —(CH₂)₂— I.a.868 Cl F F H F Cl —(CH₂)₂— I.a.869 FCl F H F Cl —(CH₂)₂— I.a.870 Cl F F H F Cl —(CH₂)₂— I.a.871 CN F F H FCl —(CH₂)₂— I.a.872 F CN F H F Cl —(CH₂)₂— I.a.873 CN F F H F Cl—(CH₂)₂— I.a.874 F F H F F Cl —(CH₂)₂— I.a.875 Cl F H F F Cl —(CH₂)₂—I.a.876 F Cl H F F Cl —(CH₂)₂— I.a.877 CN F H F F Cl —(CH₂)₂— I.a.878 FCN H F F Cl —(CH₂)₂— I.a.879 F F F F F Cl —(CH₂)₂— I.a.880 Cl F F F F Cl—(CH₂)₂— I.a.881 F Cl F F F Cl —(CH₂)₂— I.a.882 CN F F F F Cl —(CH₂)₂—I.a.883 F CN F F F Cl —(CH₂)₂— I.a.884 H F F F F Cl —(CH₂)₂— I.a.885 F FBr F F Cl —(CH₂)₂— I.a.886 F F C≡CH F F Cl —(CH₂)₂— I.a.887 CF₃ Cl H H FCl —(CH₂)₂— I.a.888 F F I F F Cl —(CH₂)₂— I.a.889 F H H H F Cl —(CH₂)₃—I.a.890 Cl H H H F Cl —(CH₂)₃— I.a.891 Br H H H F Cl —(CH₂)₃— I.a.892 CNH H H F Cl —(CH₂)₃— I.a.893 CH₃ H H H F Cl —(CH₂)₃— I.a.894 F H H F F Cl—(CH₂)₃— I.a.895 Cl H H F F Cl —(CH₂)₃— I.a.896 F H H Cl F Cl —(CH₂)₃—I.a.897 Cl H H F F Cl —(CH₂)₃— I.a.898 CN H H F F Cl —(CH₂)₃— I.a.899 FH H CN F Cl —(CH₂)₃— I.a.900 CN H H F F Cl —(CH₂)₃— I.a.901 F H F H F Cl—(CH₂)₃— I.a.902 Cl H F H F Cl —(CH₂)₃— I.a.903 CN H F H F Cl —(CH₂)₃—I.a.904 F F F H F Cl —(CH₂)₃— I.a.905 Cl F F H F Cl —(CH₂)₃— I.a.906 FCl F H F Cl —(CH₂)₃— I.a.907 Cl F F H F Cl —(CH₂)₃— I.a.908 CN F F H FCl —(CH₂)₃— I.a.909 F CN F H F Cl —(CH₂)₃— I.a.910 CN F F H F Cl—(CH₂)₃— I.a.911 F F H F F Cl —(CH₂)₃— I.a.912 Cl F H F F Cl —(CH₂)₃—I.a.913 F Cl H F F Cl —(CH₂)₃— I.a.914 CN F H F F Cl —(CH₂)₃— I.a.915 FCN H F F Cl —(CH₂)₃— I.a.916 F F F F F Cl —(CH₂)₃— I.a.917 Cl F F F F Cl—(CH₂)₃— I.a.918 F Cl F F F Cl —(CH₂)₃— I.a.919 CN F F F F Cl —(CH₂)₃—I.a.920 F CN F F F Cl —(CH₂)₃— I.a.921 H F F F F Cl —(CH₂)₃— I.a.922 F FBr F F Cl —(CH₂)₃— I.a.923 F F C≡CH F F Cl —(CH₂)₃— I.a.924 CF₃ Cl H H FCl —(CH₂)₃— I.a.925 F F I F F Cl —(CH₂)₃— I.a.926 F H H H F Cl —(CH₂)₄—I.a.927 Cl H H H F Cl —(CH₂)₄— I.a.928 Br H H H F Cl —(CH₂)₄— I.a.929 CNH H H F Cl —(CH₂)₄— I.a.930 CH₃ H H H F Cl —(CH₂)₄— I.a.931 F H H F F Cl—(CH₂)₄— I.a.932 Cl H H F F Cl —(CH₂)₄— I.a.933 F H H Cl F Cl —(CH₂)₄—I.a.934 Cl H H F F Cl —(CH₂)₄— I.a.935 CN H H F F Cl —(CH₂)₄— I.a.936 FH H CN F Cl —(CH₂)₄— I.a.937 CN H H F F Cl —(CH₂)₄— I.a.938 F H F H F Cl—(CH₂)₄— I.a.939 Cl H F H F Cl —(CH₂)₄— I.a.940 CN H F H F Cl —(CH₂)₄—I.a.941 F F F H F Cl —(CH₂)₄— I.a.942 Cl F F H F Cl —(CH₂)₄— I.a.943 FCl F H F Cl —(CH₂)₄— I.a.944 Cl F F H F Cl —(CH₂)₄— I.a.945 CN F F H FCl —(CH₂)₄— I.a.946 F CN F H F Cl —(CH₂)₄— I.a.947 CN F F H F Cl—(CH₂)₄— I.a.948 F F H F F Cl —(CH₂)₄— I.a.949 Cl F H F F Cl —(CH₂)₄—I.a.950 F Cl H F F Cl —(CH₂)₄— I.a.951 CN F H F F Cl —(CH₂)₄— I.a.952 FCN H F F Cl —(CH₂)₄— I.a.953 F F F F F Cl —(CH₂)₄— I.a.954 Cl F F F F Cl—(CH₂)₄— I.a.955 F Cl F F F Cl —(CH₂)₄— I.a.956 CN F F F F Cl —(CH₂)₄—I.a.957 F CN F F F Cl —(CH₂)₄— I.a.958 H F F F F Cl —(CH₂)₄— I.a.959 F FBr F F Cl —(CH₂)₄— I.a.960 F F C≡CH F F Cl —(CH₂)₄— I.a.961 CF₃ Cl H H FCl —(CH₂)₄— I.a.962 F F I F F Cl —(CH₂)₄— I.a.963 F H H H F Cl —(CH₂)₅—I.a.964 Cl H H H F Cl —(CH₂)₅— I.a.965 Br H H H F Cl —(CH₂)₅— I.a.966 CNH H H F Cl —(CH₂)₅— I.a.967 CH₃ H H H F Cl —(CH₂)₅— I.a.968 F H H F F Cl—(CH₂)₅— I.a.969 Cl H H F F Cl —(CH₂)₅— I.a.970 F H H Cl F Cl —(CH₂)₅—I.a.971 Cl H H F F Cl —(CH₂)₅— I.a.972 CN H H F F Cl —(CH₂)₅— I.a.973 FH H CN F Cl —(CH₂)₅— I.a.974 CN H H F F Cl —(CH₂)₅— I.a.975 F H F H F Cl—(CH₂)₅— I.a.976 Cl H F H F Cl —(CH₂)₅— I.a.977 CN H F H F Cl —(CH₂)₅—I.a.978 F F F H F Cl —(CH₂)₅— I.a.979 Cl F F H F Cl —(CH₂)₅— I.a.980 FCl F H F Cl —(CH₂)₅— I.a.981 Cl F F H F Cl —(CH₂)₅— I.a.982 CN F F H FCl —(CH₂)₅— I.a.983 F CN F H F Cl —(CH₂)₅— I.a.984 CN F F H F Cl—(CH₂)₅— I.a.985 F F H F F Cl —(CH₂)₅— I.a.986 Cl F H F F Cl —(CH₂)₅—I.a.987 F Cl H F F Cl —(CH₂)₅— I.a.988 CN F H F F Cl —(CH₂)₅— I.a.989 FCN H F F Cl —(CH₂)₅— I.a.990 F F F F F Cl —(CH₂)₅— I.a.991 Cl F F F F Cl—(CH₂)₅— I.a.992 F Cl F F F Cl —(CH₂)₅— I.a.993 CN F F F F Cl —(CH₂)₅—I.a.994 F CN F F F Cl —(CH₂)₅— I.a.995 H F F F F Cl —(CH₂)₅— I.a.996 F FBr F F Cl —(CH₂)₅— I.a.997 F F C≡CH F F Cl —(CH₂)₅— I.a.998 CF₃ Cl H H FCl —(CH₂)₅— I.a.999 F F I F F Cl —(CH₂)₅— I.a.1000 F H H H F C₂H₅ CH₃ HI.a.1001 Cl H H H F C₂H₅ CH₃ H I.a.1002 Br H H H F C₂H₅ CH₃ H I.a.1003CN H H H F C₂H₅ CH₃ H I.a.1004 CH₃ H H H F C₂H₅ CH₃ H I.a.1005 F H H F FC₂H₅ CH₃ H I.a.1006 Cl H H F F C₂H₅ CH₃ H I.a.1007 F H H Cl F C₂H₅ CH₃ HI.a.1008 Cl H H F F C₂H₅ CH₃ H I.a.1009 CN H H F F C₂H₅ CH₃ H I.a.1010 FH H CN F C₂H₅ CH₃ H I.a.1011 CN H H F F C₂H₅ CH₃ H I.a.1012 F H F H FC₂H₅ CH₃ H I.a.1013 Cl H F H F C₂H₅ CH₃ H I.a.1014 CN H F H F C₂H₅ CH₃ HI.a.1015 F F F H F C₂H₅ CH₃ H I.a.1016 Cl F F H F C₂H₅ CH₃ H I.a.1017 FCl F H F C₂H₅ CH₃ H I.a.1018 Cl F F H F C₂H₅ CH₃ H I.a.1019 CN F F H FC₂H₅ CH₃ H I.a.1020 F CN F H F C₂H₅ CH₃ H I.a.1021 CN F F H F C₂H₅ CH₃ HI.a.1022 F F H F F C₂H₅ CH₃ H I.a.1023 Cl F H F F C₂H₅ CH₃ H I.a.1024 FCl H F F C₂H₅ CH₃ H I.a.1025 CN F H F F C₂H₅ CH₃ H I.a.1026 F CN H F FC₂H₅ CH₃ H I.a.1027 F F F F F C₂H₅ CH₃ H I.a.1028 Cl F F F F C₂H₅ CH₃ HI.a.1029 F Cl F F F C₂H₅ CH₃ H I.a.1030 CN F F F F C₂H₅ CH₃ H I.a.1031 FCN F F F C₂H₅ CH₃ H I.a.1032 H F F F F C₂H₅ CH₃ H I.a.1033 F F Br F FC₂H₅ CH₃ H I.a.1034 F F C≡CH F F C₂H₅ CH₃ H I.a.1035 CF₃ Cl H H F C₂H₅CH₃ H I.a.1036 F F I F F C₂H₅ CH₃ H I.a.1037 F H H H F C₂H₅ C₂H₅ HI.a.1038 Cl H H H F C₂H₅ C₂H₅ H I.a.1039 Br H H H F C₂H₅ C₂H₅ H I.a.1040CN H H H F C₂H₅ C₂H₅ H I.a.1041 CH₃ H H H F C₂H₅ C₂H₅ H I.a.1042 F H H FF C₂H₅ C₂H₅ H I.a.1043 Cl H H F F C₂H₅ C₂H₅ H I.a.1044 F H H Cl F C₂H₅C₂H₅ H I.a.1045 Cl H H F F C₂H₅ C₂H₅ H I.a.1046 CN H H F F C₂H₅ C₂H₅ HI.a.1047 F H H CN F C₂H₅ C₂H₅ H I.a.1048 CN H H F F C₂H₅ C₂H₅ H I.a.1049F H F H F C₂H₅ C₂H₅ H I.a.1050 Cl H F H F C₂H₅ C₂H₅ H I.a.1051 CN H F HF C₂H₅ C₂H₅ H I.a.1052 F F F H F C₂H₅ C₂H₅ H I.a.1053 Cl F F H F C₂H₅C₂H₅ H I.a.1054 F Cl F H F C₂H₅ C₂H₅ H I.a.1055 Cl F F H F C₂H₅ C₂H₅ HI.a.1056 CN F F H F C₂H₅ C₂H₅ H I.a.1057 F CN F H F C₂H₅ C₂H₅ H I.a.1058CN F F H F C₂H₅ C₂H₅ H I.a.1059 F F H F F C₂H₅ C₂H₅ H I.a.1060 Cl F H FF C₂H₅ C₂H₅ H I.a.1061 F Cl H F F C₂H₅ C₂H₅ H I.a.1062 CN F H F F C₂H₅C₂H₅ H I.a.1063 F CN H F F C₂H₅ C₂H₅ H I.a.1064 F F F F F C₂H₅ C₂H₅ HI.a.1065 Cl F F F F C₂H₅ C₂H₅ H I.a.1066 F Cl F F F C₂H₅ C₂H₅ H I.a.1067CN F F F F C₂H₅ C₂H₅ H I.a.1068 F CN F F F C₂H₅ C₂H₅ H I.a.1069 H F F FF C₂H₅ C₂H₅ H I.a.1070 F F Br F F C₂H₅ C₂H₅ H I.a.1071 F F C≡CH F F C₂H₅C₂H₅ H I.a.1072 CF₃ Cl H H F C₂H₅ C₂H₅ H I.a.1073 F F I F F C₂H₅ C₂H₅ HI.a.1074 F H H H F C₂H₅ C₂H₅ CH₃ I.a.1075 Cl H H H F C₂H₅ C₂H₅ CH₃I.a.1076 Br H H H F C₂H₅ C₂H₅ CH₃ I.a.1077 CN H H H F C₂H₅ C₂H₅ CH₃I.a.1078 CH₃ H H H F C₂H₅ C₂H₅ CH₃ I.a.1079 F H H F F C₂H₅ C₂H₅ CH₃I.a.1080 Cl H H F F C₂H₅ C₂H₅ CH₃ I.a.1081 F H H Cl F C₂H₅ C₂H₅ CH₃I.a.1082 Cl H H F F C₂H₅ C₂H₅ CH₃ I.a.1083 CN H H F F C₂H₅ C₂H₅ CH₃I.a.1084 F H H CN F C₂H₅ C₂H₅ CH₃ I.a.1085 CN H H F F C₂H₅ C₂H₅ CH₃I.a.1086 F H F H F C₂H₅ C₂H₅ CH₃ I.a.1087 Cl H F H F C₂H₅ C₂H₅ CH₃I.a.1088 CN H F H F C₂H₅ C₂H₅ CH₃ I.a.1089 F F F H F C₂H₅ C₂H₅ CH₃I.a.1090 Cl F F H F C₂H₅ C₂H₅ CH₃ I.a.1091 F Cl F H F C₂H₅ C₂H₅ CH₃I.a.1092 Cl F F H F C₂H₅ C₂H₅ CH₃ I.a.1093 CN F F H F C₂H₅ C₂H₅ CH₃I.a.1094 F CN F H F C₂H₅ C₂H₅ CH₃ I.a.1095 CN F F H F C₂H₅ C₂H₅ CH₃I.a.1096 F F H F F C₂H₅ C₂H₅ CH₃ I.a.1097 Cl F H F F C₂H₅ C₂H₅ CH₃I.a.1098 F Cl H F F C₂H₅ C₂H₅ CH₃ I.a.1099 CN F H F F C₂H₅ C₂H₅ CH₃I.a.1100 F CN H F F C₂H₅ C₂H₅ CH₃ I.a.1101 F F F F F C₂H₅ C₂H₅ CH₃I.a.1102 Cl F F F F C₂H₅ C₂H₅ CH₃ I.a.1103 F Cl F F F C₂H₅ C₂H₅ CH₃I.a.1104 CN F F F F C₂H₅ C₂H₅ CH₃ I.a.1105 F CN F F F C₂H₅ C₂H₅ CH₃I.a.1106 H F F F F C₂H₅ C₂H₅ CH₃ I.a.1107 F F Br F F C₂H₅ C₂H₅ CH₃I.a.1108 F F C≡CH F F C₂H₅ C₂H₅ CH₃ I.a.1109 CF₃ Cl H H F C₂H₅ C₂H₅ CH₃I.a.1110 F F I F F C₂H₅ C₂H₅ CH₃ I.a.1111 F H H H F C₂H₅ CH₃ CH₃I.a.1112 Cl H H H F C₂H₅ CH₃ CH₃ I.a.1113 Br H H H F C₂H₅ CH₃ CH₃I.a.1114 CN H H H F C₂H₅ CH₃ CH₃ I.a.1115 CH₃ H H H F C₂H₅ CH₃ CH₃I.a.1116 F H H F F C₂H₅ CH₃ CH₃ I.a.1117 Cl H H F F C₂H₅ CH₃ CH₃I.a.1118 F H H Cl F C₂H₅ CH₃ CH₃ I.a.1119 Cl H H F F C₂H₅ CH₃ CH₃I.a.1120 CN H H F F C₂H₅ CH₃ CH₃ I.a.1121 F H H CN F C₂H₅ CH₃ CH₃I.a.1122 CN H H F F C₂H₅ CH₃ CH₃ I.a.1123 F H F H F C₂H₅ CH₃ CH₃I.a.1124 Cl H F H F C₂H₅ CH₃ CH₃ I.a.1125 CN H F H F C₂H₅ CH₃ CH₃I.a.1126 F F F H F C₂H₅ CH₃ CH₃ I.a.1127 Cl F F H F C₂H₅ CH₃ CH₃I.a.1128 F Cl F H F C₂H₅ CH₃ CH₃ I.a.1129 Cl F F H F C₂H₅ CH₃ CH₃I.a.1130 CN F F H F C₂H₅ CH₃ CH₃ I.a.1131 F CN F H F C₂H₅ CH₃ CH₃I.a.1132 CN F F H F C₂H₅ CH₃ CH₃ I.a.1133 F F H F F C₂H₅ CH₃ CH₃I.a.1134 Cl F H F F C₂H₅ CH₃ CH₃ I.a.1135 F Cl H F F C₂H₅ CH₃ CH₃I.a.1136 CN F H F F C₂H₅ CH₃ CH₃ I.a.1137 F CN H F F C₂H₅ CH₃ CH₃I.a.1138 F F F F F C₂H₅ CH₃ CH₃ I.a.1139 Cl F F F F C₂H₅ CH₃ CH₃I.a.1140 F Cl F F F C₂H₅ CH₃ CH₃ I.a.1141 CN F F F F C₂H₅ CH₃ CH₃I.a.1142 F CN F F F C₂H₅ CH₃ CH₃ I.a.1143 H F F F F C₂H₅ CH₃ CH₃I.a.1144 F F Br F F C₂H₅ CH₃ CH₃ I.a.1145 F F C≡CH F F C₂H₅ CH₃ CH₃I.a.1146 CF₃ Cl H H F C₂H₅ CH₃ CH₃ I.a.1147 F F I F F C₂H₅ CH₃ CH₃I.a.1148 F H H H F Cl CH₃ H I.a.1149 Cl H H H F Cl CH₃ H I.a.1150 Br H HH F Cl CH₃ H I.a.1151 CN H H H F Cl CH₃ H I.a.1152 CH₃ H H H F Cl CH₃ HI.a.1153 F H H F F Cl CH₃ H I.a.1154 Cl H H F F Cl CH₃ H I.a.1155 F H HCl F Cl CH₃ H I.a.1156 Cl H H F F Cl CH₃ H I.a.1157 CN H H F F Cl CH₃ HI.a.1158 F H H CN F Cl CH₃ H I.a.1159 CN H H F F Cl CH₃ H I.a.1160 F H FH F Cl CH₃ H I.a.1161 Cl H F H F Cl CH₃ H I.a.1162 CN H F H F Cl CH₃ HI.a.1163 F F F H F Cl CH₃ H I.a.1164 Cl F F H F Cl CH₃ H I.a.1165 F Cl FH F Cl CH₃ H I.a.1166 Cl F F H F Cl CH₃ H I.a.1167 CN F F H F Cl CH₃ HI.a.1168 F CN F H F Cl CH₃ H I.a.1169 CN F F H F Cl CH₃ H I.a.1170 F F HF F Cl CH₃ H I.a.1171 Cl F H F F Cl CH₃ H I.a.1172 F Cl H F F Cl CH₃ HI.a.1173 CN F H F F Cl CH₃ H I.a.1174 F CN H F F Cl CH₃ H I.a.1175 F F FF F Cl CH₃ H I.a.1176 Cl F F F F Cl CH₃ H I.a.1177 F Cl F F F Cl CH₃ HI.a.1178 CN F F F F Cl CH₃ H I.a.1179 F CN F F F Cl CH₃ H I.a.1180 H F FF F Cl CH₃ H I.a.1181 F F Br F F Cl CH₃ H I.a.1182 F F C≡CH F F Cl CH₃ HI.a.1183 CF₃ Cl H H F Cl CH₃ H I.a.1184 F F I F F Cl CH₃ H I.a.1185 F HH H F CH₂Cl Cl CH₃ I.a.1186 Cl H H H F CH₂Cl Cl CH₃ I.a.1187 Br H H H FCH₂Cl Cl CH₃ I.a.1188 CN H H H F CH₂Cl Cl CH₃ I.a.1189 CH₃ H H H F CH₂ClCl CH₃ I.a.1190 F H H F F CH₂Cl Cl CH₃ I.a.1191 Cl H H F F CH₂Cl Cl CH₃I.a.1192 F H H Cl F CH₂Cl Cl CH₃ I.a.1193 Cl H H F F CH₂Cl Cl CH₃I.a.1194 CN H H F F CH₂Cl Cl CH₃ I.a.1195 F H H CN F CH₂Cl Cl CH₃I.a.1196 CN H H F F CH₂Cl Cl CH₃ I.a.1197 F H F H F CH₂Cl Cl CH₃I.a.1198 Cl H F H F CH₂Cl Cl CH₃ I.a.1199 CN H F H F CH₂Cl Cl CH₃I.a.1200 F F F H F CH₂Cl Cl CH₃ I.a.1201 Cl F F H F CH₂Cl Cl CH₃I.a.1202 F Cl F H F CH₂Cl Cl CH₃ I.a.1203 Cl F F H F CH₂Cl Cl CH₃I.a.1204 CN F F H F CH₂Cl Cl CH₃ I.a.1205 F CN F H F CH₂Cl Cl CH₃I.a.1206 CN F F H F CH₂Cl Cl CH₃ I.a.1207 F F H F F CH₂Cl Cl CH₃I.a.1208 Cl F H F F CH₂Cl Cl CH₃ I.a.1209 F Cl H F F CH₂Cl Cl CH₃I.a.1210 CN F H F F CH₂Cl Cl CH₃ I.a.1211 F CN H F F CH₂Cl Cl CH₃I.a.1212 F F F F F CH₂Cl Cl CH₃ I.a.1213 Cl F F F F CH₂Cl Cl CH₃I.a.1214 F Cl F F F CH₂Cl Cl CH₃ I.a.1215 CN F F F F CH₂Cl Cl CH₃I.a.1216 F CN F F F CH₂Cl Cl CH₃ I.a.1217 H F F F F CH₂Cl Cl CH₃I.a.1218 F F Br F F CH₂Cl Cl CH₃ I.a.1219 F F C≡CH F F CH₂Cl Cl CH₃I.a.1220 CF₃ Cl H H F CH₂Cl Cl CH₃ I.a.1221 F F I F F CH₂Cl Cl CH₃I.a.1222 F H H H F CN CH₃ CH₃ I.a.1223 Cl H H H F CN CH₃ CH₃ I.a.1224 BrH H H F CN CH₃ CH₃ I.a.1225 CN H H H F CN CH₃ CH₃ I.a.1226 CH₃ H H H FCN CH₃ CH₃ I.a.1227 F H H F F CN CH₃ CH₃ I.a.1228 Cl H H F F CN CH₃ CH₃I.a.1229 F H H Cl F CN CH₃ CH₃ I.a.1230 Cl H H F F CN CH₃ CH₃ I.a.1231CN H H F F CN CH₃ CH₃ I.a.1232 F H H CN F CN CH₃ CH₃ I.a.1233 CN H H F FCN CH₃ CH₃ I.a.1234 F H F H F CN CH₃ CH₃ I.a.1235 Cl H F H F CN CH₃ CH₃I.a.1236 CN H F H F CN CH₃ CH₃ I.a.1237 F F F H F CN CH₃ CH₃ I.a.1238 ClF F H F CN CH₃ CH₃ I.a.1239 F Cl F H F CN CH₃ CH₃ I.a.1240 Cl F F H F CNCH₃ CH₃ I.a.1241 CN F F H F CN CH₃ CH₃ I.a.1242 F CN F H F CN CH₃ CH₃I.a.1243 CN F F H F CN CH₃ CH₃ I.a.1244 F F H F F CN CH₃ CH₃ I.a.1245 ClF H F F CN CH₃ CH₃ I.a.1246 F Cl H F F CN CH₃ CH₃ I.a.1247 CN F H F F CNCH₃ CH₃ I.a.1248 F CN H F F CN CH₃ CH₃ I.a.1249 F F F F F CN CH₃ CH₃I.a.1250 Cl F F F F CN CH₃ CH₃ I.a.1251 F Cl F F F CN CH₃ CH₃ I.a.1252CN F F F F CN CH₃ CH₃ I.a.1253 F CN F F F CN CH₃ CH₃ I.a.1254 H F F F FCN CH₃ CH₃ I.a.1255 F F Br F F CN CH₃ CH₃ I.a.1256 F F C≡CH F F CN CH₃CH₃ I.a.1257 CF₃ Cl H H F CN CH₃ CH₃ I.a.1258 F F I F F CN CH₃ CH₃I.a.1259 F H H H F OCH₃ H H I.a.1260 Cl H H H F OCH₃ H H I.a.1261 Br H HH F OCH₃ H H I.a.1262 CN H H H F OCH₃ H H I.a.1263 CH₃ H H H F OCH₃ H HI.a.1264 F H H F F OCH₃ H H I.a.1265 Cl H H F F OCH₃ H H I.a.1266 F H HCl F OCH₃ H H I.a.1267 Cl H H F F OCH₃ H H I.a.1268 CN H H F F OCH₃ H HI.a.1269 F H H CN F OCH₃ H H I.a.1270 CN H H F F OCH₃ H H I.a.1271 F H FH F OCH₃ H H I.a.1272 Cl H F H F OCH₃ H H I.a.1273 CN H F H F OCH₃ H HI.a.1274 F F F H F OCH₃ H H I.a.1275 Cl F F H F OCH₃ H H I.a.1276 F Cl FH F OCH₃ H H I.a.1277 Cl F F H F OCH₃ H H I.a.1278 CN F F H F OCH₃ H HI.a.1279 F CN F H F OCH₃ H H I.a.1280 CN F F H F OCH₃ H H I.a.1281 F F HF F OCH₃ H H I.a.1282 Cl F H F F OCH₃ H H I.a.1283 F Cl H F F OCH₃ H HI.a.1284 CN F H F F OCH₃ H H I.a.1285 F CN H F F OCH₃ H H I.a.1286 F F FF F OCH₃ H H I.a.1287 Cl F F F F OCH₃ H H I.a.1288 F Cl F F F OCH₃ H HI.a.1289 CN F F F F OCH₃ H H I.a.1290 F CN F F F OCH₃ H H I.a.1291 H F FF F OCH₃ H H I.a.1292 F F Br F F OCH₃ H H I.a.1293 F F C≡CH F F OCH₃ H HI.a.1294 CF₃ Cl H H F OCH₃ H H I.a.1295 F F I F F OCH₃ H H I.a.1296 F HH H F OCH₃ CH₃ H I.a.1297 Cl H H H F OCH₃ CH₃ H I.a.1298 Br H H H F OCH₃CH₃ H I.a.1299 CN H H H F OCH₃ CH₃ H I.a.1300 CH₃ H H H F OCH₃ CH₃ HI.a.1301 F H H F F OCH₃ CH₃ H I.a.1302 Cl H H F F OCH₃ CH₃ H I.a.1303 FH H Cl F OCH₃ CH₃ H I.a.1304 Cl H H F F OCH₃ CH₃ H I.a.1305 CN H H F FOCH₃ CH₃ H I.a.1306 F H H CN F OCH₃ CH₃ H I.a.1307 CN H H F F OCH₃ CH₃ HI.a.1308 F H F H F OCH₃ CH₃ H I.a.1309 Cl H F H F OCH₃ CH₃ H I.a.1310 CNH F H F OCH₃ CH₃ H I.a.1311 F F F H F OCH₃ CH₃ H I.a.1312 Cl F F H FOCH₃ CH₃ H I.a.1313 F Cl F H F OCH₃ CH₃ H I.a.1314 Cl F F H F OCH₃ CH₃ HI.a.1315 CN F F H F OCH₃ CH₃ H I.a.1316 F CN F H F OCH₃ CH₃ H I.a.1317CN F F H F OCH₃ CH₃ H I.a.1318 F F H F F OCH₃ CH₃ H I.a.1319 Cl F H F FOCH₃ CH₃ H I.a.1320 F Cl H F F OCH₃ CH₃ H I.a.1321 CN F H F F OCH₃ CH₃ HI.a.1322 F CN H F F OCH₃ CH₃ H I.a.1323 F F F F F OCH₃ CH₃ H I.a.1324 ClF F F F OCH₃ CH₃ H I.a.1325 F Cl F F F OCH₃ CH₃ H I.a.1326 CN F F F FOCH₃ CH₃ H I.a.1327 F CN F F F OCH₃ CH₃ H I.a.1328 H F F F F OCH₃ CH₃ HI.a.1329 F F Br F F OCH₃ CH₃ H I.a.1330 F F C≡CH F F OCH₃ CH₃ H I.a.1331CF₃ Cl H H F OCH₃ CH₃ H I.a.1332 F F I F F OCH₃ CH₃ H I.a.1333 F H H H FOCH₃ CH₃ CH₃ I.a.1334 Cl H H H F OCH₃ CH₃ CH₃ I.a.1335 Br H H H F OCH₃CH₃ CH₃ I.a.1336 CN H H H F OCH₃ CH₃ CH₃ I.a.1337 CH₃ H H H F OCH₃ CH₃CH₃ I.a.1338 F H H F F OCH₃ CH₃ CH₃ I.a.1339 Cl H H F F OCH₃ CH₃ CH₃I.a.1340 F H H Cl F OCH₃ CH₃ CH₃ I.a.1341 Cl H H F F OCH₃ CH₃ CH₃I.a.1342 CN H H F F OCH₃ CH₃ CH₃ I.a.1343 F H H CN F OCH₃ CH₃ CH₃I.a.1344 CN H H F F OCH₃ CH₃ CH₃ I.a.1345 F H F H F OCH₃ CH₃ CH₃I.a.1346 Cl H F H F OCH₃ CH₃ CH₃ I.a.1347 CN H F H F OCH₃ CH₃ CH₃I.a.1348 F F F H F OCH₃ CH₃ CH₃ I.a.1349 Cl F F H F OCH₃ CH₃ CH₃I.a.1350 F Cl F H F OCH₃ CH₃ CH₃ I.a.1351 Cl F F H F OCH₃ CH₃ CH₃I.a.1352 CN F F H F OCH₃ CH₃ CH₃ I.a.1353 F CN F H F OCH₃ CH₃ CH₃I.a.1354 CN F F H F OCH₃ CH₃ CH₃ I.a.1355 F F H F F OCH₃ CH₃ CH₃I.a.1356 Cl F H F F OCH₃ CH₃ CH₃ I.a.1357 F Cl H F F OCH₃ CH₃ CH₃I.a.1358 CN F H F F OCH₃ CH₃ CH₃ I.a.1359 F CN H F F OCH₃ CH₃ CH₃I.a.1360 F F F F F OCH₃ CH₃ CH₃ I.a.1361 Cl F F F F OCH₃ CH₃ CH₃I.a.1362 F Cl F F F OCH₃ CH₃ CH₃ I.a.1363 CN F F F F OCH₃ CH₃ CH₃I.a.1364 F CN F F F OCH₃ CH₃ CH₃ I.a.1365 H F F F F OCH₃ CH₃ CH₃I.a.1366 F F Br F F OCH₃ CH₃ CH₃ I.a.1367 F F C≡CH F F OCH₃ CH₃ CH₃I.a.1368 CF₃ Cl H H F OCH₃ CH₃ CH₃ I.a.1369 F F I F F OCH₃ CH₃ CH₃I.a.1370 F H H H F H —O(CH₂)₃— I.a.1371 Cl H H H F H —O(CH₂)₃— I.a.1372Br H H H F H —O(CH₂)₃— I.a.1373 CN H H H F H —O(CH₂)₃— I.a.1374 CH₃ H HH F H —O(CH₂)₃— I.a.1375 F H H F F H —O(CH₂)₃— I.a.1376 Cl H H F F H—O(CH₂)₃— I.a.1377 F H H Cl F H —O(CH₂)₃— I.a.1378 Cl H H F F H—O(CH₂)₃— I.a.1379 CN H H F F H —O(CH₂)₃— I.a.1380 F H H CN F H—O(CH₂)₃— I.a.1381 CN H H F F H —O(CH₂)₃— I.a.1382 F H F H F H —O(CH₂)₃—I.a.1383 Cl H F H F H —O(CH₂)₃— I.a.1384 CN H F H F H —O(CH₂)₃— I.a.1385F F F H F H —O(CH₂)₃— I.a.1386 Cl F F H F H —O(CH₂)₃— I.a.1387 F Cl F HF H —O(CH₂)₃— I.a.1388 Cl F F H F H —O(CH₂)₃— I.a.1389 CN F F H F H—O(CH₂)₃— I.a.1390 F CN F H F H —O(CH₂)₃— I.a.1391 CN F F H F H—O(CH₂)₃— I.a.1392 F F H F F H —O(CH₂)₃— I.a.1393 Cl F H F F H —O(CH₂)₃—I.a.1394 F Cl H F F H —O(CH₂)₃— I.a.1395 CN F H F F H —O(CH₂)₃— I.a.1396F CN H F F H —O(CH₂)₃— I.a.1397 F F F F F H —O(CH₂)₃— I.a.1398 Cl F F FF H —O(CH₂)₃— I.a.1399 F Cl F F F H —O(CH₂)₃— I.a.1400 CN F F F F H—O(CH₂)₃— I.a.1401 F CN F F F H —O(CH₂)₃— I.a.1402 H F F F F H —O(CH₂)₃—I.a.1403 F F Br F F H —O(CH₂)₃— I.a.1404 F F C≡CH F F H —O(CH₂)₃—I.a.1405 CF₃ Cl H H F H —O(CH₂)₃— I.a.1406 F F I F F H —O(CH₂)₃—

In another preferred embodiment, the azines useful for the presentinvention are azines of formula (I)

wherein

-   A is heteroaryl, which is substituted by 1, 2, 3, 4, 5 or 6    substituents R^(A) selected from the group consisting of halogen,    OH, CN, amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,    C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)-carbonyl, (C₁-C₆-alkyl)-carbonyloxy,    C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and    cycloaliphatic parts of the 22 aforementioned radicals are    unsubstituted, partly or completely halogenated and where the    cycloaliphatic parts of the last 4 mentioned radicals may carry 1,    2, 3, 4, 5 or 6 methyl groups;-   R¹ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,    C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,    (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and    (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts    of the 14 aforementioned radicals are unsubstituted, partly or    completely halogenated,    -   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl, phenylaminosulfonyl,        phenylcarbonyl and phenoxycarbonyl,    -   wherein phenyl in the last 6 mentioned radicals are        unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or        different substituents selected from the group consisting of        halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and        C₁-C₆-haloalkoxy;-   R² is H, halogen, OH, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy,    C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy or    (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and    cycloaliphatic parts of the 9 aforementioned radicals are    unsubstituted, partly or completely halogenated,    -   phenyl, phenyl-C₁-C₆-alkyl,    -   wherein phenyl in the last 2 mentioned radicals are        unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or        different substituents selected from the group consisting of        halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and        C₁-C₆-haloalkoxy;-   R³ is selected from the group consisting of H, halogen, CN,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;-   R⁴ is selected from the group consisting of H, halogen, CN,    C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl, C₃-C₆-cycloalkyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkenyl and    C₁-C₆-alkoxy-C₁-C₆-alkyl, where the aliphatic and cycloaliphatic    parts of the 7 aforementioned radicals are unsubstituted, partly or    completely halogenated; or-   R³ and R⁴ together with the carbon atom to which they are attached    form a moiety selected from the group consisting of carbonyl,    C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl and three- to    six-membered heterocyclyl,    -   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, or three- to        six-membered heterocyclyl is unsubstituted or substituted by one        to three substituents selected from halogen, CN, C₁-C₆-alkyl and        C₁-C₆-alkoxy; and-   R⁵ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,    C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,    (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and    (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts    of the 14 aforementioned radicals are unsubstituted, partly or    completely halogenated,    -   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl, phenylaminosulfonyl,        phenylcarbonyl and phenoxycarbonyl,    -   wherein phenyl in the last 6 mentioned radicals are        unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or        different substituents selected from the group consisting of        halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and        C₁-C₆-haloalkoxy;        and wherein the variables A, R¹, R², R³, R⁴ and R⁵ are in        particular:-   A is heteroaryl, which is substituted by 1, 2, 3, 4, 5 or 6    substituents R^(A) selected from the group consisting of halogen,    OH, CN, amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,    C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)-carbonyl, (C₁-C₆-alkyl)-carbonyloxy,    C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and    cycloaliphatic parts of the 22 aforementioned radicals are    unsubstituted, partly or completely halogenated and where the    cycloaliphatic parts of the last 4 mentioned radicals may carry 1,    2, 3, 4, 5 or 6 methyl groups;-   R¹ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,    C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,    (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and    (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts    of the 14 aforementioned radicals are unsubstituted, partly or    completely halogenated,    -   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl, phenylaminosulfonyl,        phenylcarbonyl and phenoxycarbonyl,    -   wherein phenyl in the last 6 mentioned radicals are        unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or        different substituents selected from the group consisting of        halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and        C₁-C₆-haloalkoxy;-   R² is H, halogen, OH, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy,    C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy or    (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and    cycloaliphatic parts of the 9 aforementioned radicals are    unsubstituted, partly or completely halogenated or phenyl, wherein    phenyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 identical    or different substituents selected from the group consisting of    halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and    C₁-C₆-haloalkoxy;    -   R³ is selected from the group consisting of H, halogen, CN,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;    -   R⁴ is selected from the group consisting of H, halogen, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl, C₃-C₆-cycloalkyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkenyl and        C₁-C₆-alkoxy-C₁-C₆-alkyl, where the aliphatic and cycloaliphatic        parts of the 7 aforementioned radicals are unsubstituted, partly        or completely halogenated; or    -   R³ and R⁴ together with the carbon atom to which they are        attached form a moiety selected from the group consisting of        carbonyl, C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl        and three- to six-membered heterocyclyl,    -   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, or three- to        six-membered heterocyclyl is unsubstituted or substituted by one        to three substituents selected from halogen, CN, C₁-C₆-alkyl and        C₁-C₆-alkoxy; and    -   R⁵ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and        (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic        parts of the 14 aforementioned radicals are unsubstituted,        partly or completely halogenated,    -   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl, phenylaminosulfonyl,        phenylcarbonyl and phenoxycarbonyl,    -   wherein phenyl in the last 6 mentioned radicals are        unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or        different substituents selected from the group consisting of        halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and        C₁-C₆-haloalkoxy;        and wherein the variables A, R¹, R², R³, R⁴ and R⁵ are in more        particular:-   A is heteroaryl, which is substituted by 1, 2, 3, 4, 5 or 6    substituents R^(A) selected from the group consisting of halogen,    OH, CN, amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,    C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)-carbonyl, (C₁-C₆-alkyl)-carbonyloxy,    C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and    cycloaliphatic parts of the 22 aforementioned radicals are    unsubstituted, partly or completely halogenated and where the    cycloaliphatic parts of the last 4 mentioned radicals may carry 1,    2, 3, 4, 5 or 6 methyl groups;-   R¹ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,    C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,    (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and    (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts    of the 14 aforementioned radicals are unsubstituted, partly or    completely halogenated,-   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl, phenylaminosulfonyl,    phenylcarbonyl and phenoxycarbonyl,-   wherein phenyl in the last 6 mentioned radicals are unsubstituted or    substituted by 1, 2, 3, 4 or 5 identical or different substituents    selected from the group consisting of halogen, CN, NO₂, C₁-C₆-alkyl,    C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;-   R² is H, halogen, OH, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy,    C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy or    (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and    cycloaliphatic parts of the 9 aforementioned radicals are    unsubstituted, partly or completely halogenated,-   R³ is selected from the group consisting of H, halogen, CN,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;-   R⁴ is selected from the group consisting of H, halogen, CN,    C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl, C₃-C₆-cycloalkyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkenyl and    C₁-C₆-alkoxy-C₁-C₆-alkyl, where the aliphatic and cycloaliphatic    parts of the 7 aforementioned radicals are unsubstituted, partly or    completely halogenated; or-   R³ and R⁴ together with the carbon atom to which they are attached    form a moiety selected from the group consisting of carbonyl,    C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl and three- to    six-membered heterocyclyl,-   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, or three- to    six-membered heterocyclyl is unsubstituted or substituted by one to    three substituents selected from halogen, CN, C₁-C₆-alkyl and    C₁-C₆-alkoxy; and-   R⁵ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,    C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,    (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,    (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,    (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,    (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,    (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and    (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts    of the 14 aforementioned radicals are unsubstituted, partly or    completely halogenated,-   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl, phenylaminosulfonyl,    phenylcarbonyl and phenoxycarbonyl,-   wherein phenyl in the last 6 mentioned radicals are unsubstituted or    substituted by 1, 2, 3, 4 or 5 identical or different substituents    selected from the group consisting of halogen, CN, NO₂, C₁-C₆-alkyl,    C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;-   and wherein the variables A, R¹, R², R³, R⁴ and R⁵ are preferred:-   A is heteroaryl, which is substituted by one to six substituents    selected from the group consisting of halogen, CN, NO₂, C₁-C₆-alkyl,    C₁-C₆-haloalkyl, OH, C₁-C₆-alkoxy, C₁-C₆-alkylthio,    (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl, amino,    (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino, (C₁-C₆-alkyl)carbonyl,    (C₁-C₆-alkoxy)carbonyl;-   R¹ is H, CN, C₁-C₆-alkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy,    (C₁-C₆-alkyl)carbonyl, (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl    or phenylsulfonyl,-   wherein the phenyl is unsubstituted or substituted by one to five    substituents selected from the group consisting of halogen, CN, NO₂,    C₁-C₆-alkyl, C₁-C₆-haloalkyl and C₁-C₆-alkoxy;-   R² is is H, halogen, OH, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl,    C₃-C₆-alkynyl, (C₁-C₆-alkoxy)-C₁-C₆-alkyl, C₃-C₆-cycloalkyl,    C₃-C₆-cycloalkenyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,    C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy or    (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and    cycloaliphatic parts of the 9 aforementioned radicals are    unsubstituted, partly or completely halogenated-   R³ is H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl or C₁-C₆-alkoxy;-   R⁴ is H, halogen, CN, C₁-C₆-alkyl or C₁-C₆-haloalkyl; or-   R³ and R⁴ together with the carbon atom to which they are attached    form a moiety selected from the group consisting of carbonyl,    C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl and three- to    six-membered heterocyclyl,-   wherein the C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, or three- to    six-membered heterocyclyl is unsubstituted or substituted by one to    three substituents selected from halogen, CN, C₁-C₆-alkyl and    C₁-C₆-alkoxy; and-   R⁵ is H, CN, C₁-C₆-alkyl, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁-C₆-alkoxy,    (C₁-C₆-alkyl)carbonyl, (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl    or phenylsulfonyl,-   wherein the phenyl is unsubstituted or substituted by one to five    substituents selected from the group consisting of halogen, CN, NO₂,    C₁-C₆-alkyl, C₁-C₆-haloalkyl and C₁-C₆-alkoxy;    including their agriculturally acceptable salts or N-oxides.

In another preferred embodiment, the azines useful for the presentinvention comprise a diaminotriazine compound of formula (I)

-   -   wherein    -   p is 1 or 2;    -   q is 0, 1, 2 or 3 provided that p+q is 1, 2, 3 or 4;    -   Q is a chemical bond, O, S(O)_(m), CR^(q1)R^(q2), NR^(q3), C(O),        C(O)O,        -   CR^(q1)R^(q2)—O, S(O)_(m)NR^(q3) or C(O)NR^(q3),        -   wherein        -   m is 0, 1 or 2;        -   R^(q1), R^(q2) are hydrogen, halogen or C₁-C₄-alkyl;        -   R^(q3) is H, CN, C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkyl,            (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl,            (C₁-C₆-alkyl)sulfonyl, where the aliphatic parts of the 6            aforementioned radicals are unsubstituted, partly or            completely halogenated;    -   Ar is phenyl, which is unsubstituted or carries 1, 2, 3, 4 or 5        radicals R^(A) which are selected from the group consisting of        halogen, OH, CN, amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl,        C₂-C₆-alkynyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        (C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,        where the aliphatic and cycloaliphatic parts of the 22        aforementioned radicals are unsubstituted, partly or completely        halogenated and where the cycloaliphatic parts of the last 4        mentioned radicals may carry 1, 2, 3, 4, 5 or 6 methyl groups,        -   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl,            phenylaminosulfonyl, phenylaminocarbonyl,            phenyl(C₁-C₆-alkyl)aminocarbonyl, phenylcarbonyl and            phenoxycarbonyl,        -   wherein phenyl in the last 8 mentioned radicals are            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy,        -   it being possible that R^(A) are identical or different;    -   R^(a) is selected from the group consisting of hydrogen,        halogen, OH, CN, amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl,        C₂-C₆-alkynyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        (C₁-C₆-alkyl)-carbonyloxy, where the aliphatic and        cycloaliphatic parts of the 14 aforementioned radicals are        unsubstituted, partly or completely halogenated;    -   R^(b) is selected from the group consisting of halogen, OH, CN,        amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        (C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,        where the aliphatic and cycloaliphatic parts of the 22        aforementioned radicals are unsubstituted, partly or completely        halogenated and where the cycloaliphatic parts of the last 4        mentioned radicals may carry 1, 2, 3, 4, 5 or 6 methyl groups,        -   for q=2 or 3 it being possible that R^(b) are identical or            different;    -   R¹ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₃-C₆-cycloalkyl)-carbonyl,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl,        (C₁-C₆-alkyl)sulfonyl, (C₁-C₆-alkylamino)carbonyl,        di(C₁-C₆-alkyl)aminocarbonyl, (C₁-C₆-alkylamino)sulfonyl,        di(C₁-C₆-alkyl)aminosulfonyl and (C₁-C₆-alkoxy)sulfonyl, where        the aliphatic and cycloaliphatic parts of the 15 aforementioned        radicals are unsubstituted, partly or completely halogenated,        -   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl,            phenylaminosulfonyl, phenylaminocarbonyl,            phenyl(C₁-C₆-alkyl)aminocarbonyl, phenylcarbonyl and            phenoxycarbonyl,        -   wherein phenyl in the last 8 mentioned radicals are            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy;    -   R² is selected from the group consisting of H, OH, S(O)₂NH₂, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkyl)-carbonyl        C₁-C₆-alkoxy, (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and        (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic        parts of the 15 aforementioned radicals are unsubstituted,        partly or completely halogenated,        -   phenyl, phenylsulfonyl, phenylaminosulfonyl,            phenylaminocarbonyl, phenyl(C₁-C₆-alkyl)aminocarbonyl,            phenyl-C₁-C₆ alkyl, phenoxy, phenylcarbonyl and            phenoxycarbonyl,        -   wherein phenyl in the last 9 mentioned radicals is            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy;    -   X is a radical selected from the group consisting of        -   CR³R⁴R⁵,        -   phenyl, which is unsubstituted or carries 1, 2, 3, 4 or 5            radicals R^(Ar) which are identical or different;        -   NR^(3a)R^(3b),        -   OR^(3c) and        -   S(O)_(k)R^(3d) with k being 0, 1 or 2    -    wherein    -    R³ is selected from the group consisting of H, halogen, OH, CN,        C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkyl, C₃-C₆-cycloalkyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy,        C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and        cycloaliphatic parts of the 9 aforementioned radicals are        unsubstituted, partly or completely halogenated;    -    R⁴ is selected from the group consisting of H, halogen, CN,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;    -    R⁵ is selected from the group consisting of halogen, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl, C₃-C₆-cycloalkyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkenyl and        C₁-C₆-alkoxy-C₁-C₆-alkyl, where the aliphatic and cycloaliphatic        parts of the 7 aforementioned radicals are unsubstituted, partly        or completely halogenated;    -    R⁴ and R⁵ together with the carbon atom to which they are        attached form a moiety selected from the group consisting of        carbonyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, three- to        six-membered saturated or partially unsaturated heterocyclyl,        and the moiety >C═CR^(x)R^(y), where R^(x) and R^(y) are        hydrogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl;    -    R^(Ar) selected from the group consisting of halogen, OH, CN,        amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        (C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,        where the aliphatic and cycloaliphatic parts of the 22        aforementioned radicals are unsubstituted, partly or completely        halogenated and where the cycloaliphatic parts of the last 4        mentioned radicals may carry 1, 2, 3, 4, 5 or 6 methyl groups,    -    R^(3a), R^(3b), R^(3c) or R^(3d) are independently of one        another are selected from the group consisting of H, CN,        S(O)₂NH₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₃-C₆-cycloalkyl, (C₃-C₆-cycloalkyl)-C₁-C₆-alkyl,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        (C₃-C₆-cycloalkyl)-carbonyl, (C₁-C₆-alkylamino)sulfonyl,        di(C₁-C₆-alkyl)aminosulfonyl and (C₁-C₆-alkoxy)sulfonyl, where        the aliphatic and cycloaliphatic parts of the 15 aforementioned        radicals are unsubstituted, partly or completely halogenated,        phenyl, phenylsulfonyl, phenyl-C₁-C₆ alkyl, phenylaminosulfonyl,        phenylcarbonyl and phenoxycarbonyl, wherein phenyl in the last 6        mentioned radicals is unsubstituted or substituted by 1, 2, 3, 4        or 5 identical or different substituents selected from the group        consisting of halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,        C₁-C₆-alkoxy and C₁-C₆-haloalkoxy, or    -    R^(3a), R^(3b) together with the nitrogen atom, to which they        are bound, form an N-bound, mono—or bicyclic heterocyclic        radical, which may have 1, 2, 3 or 4 further heteroatoms which        are selected from N, O and S, which is unsubstituted or        substituted by one or more identical or different substituents        selected from the group consisting of halogen, CN, NO₂,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy,        -   one of R^(3a), R^(3b) may also be OH, C₁-C₆-alkoxy,            C₃-C₆-cycloalkoxy, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy            C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,            (C₁-C₆-alkoxy)-C₁-C₆-alkoxy, where the aliphatic and            cycloaliphatic parts of the 7 aforementioned radicals are            unsubstituted, partly or completely halogenated, or phenoxy,            which is unsubstituted or substituted by 1, 2, 3, 4 or 5            identical or different substituents selected from the group            consisting of halogen, CN, NO₂, C₁-C₆-alkyl,            C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;    -   including their agriculturally acceptable salts

In another preferred embodiment, the azines useful for the presentinvention comprises a diaminotriazine compound of the formula:

-   -   wherein    -   A is a fused saturated or unsaturated, 5- or 6-membered        carbocycle or a fused saturated or unsaturated, 5- or 6-membered        heterocycle having 1, 2 or 3 heteroatoms or heteroatom moieties,        selected from O, S, S(O)_(p), N or NR^(c) as ring members,        -   where the carbocycle and the heterocycle are unsubstituted            or carry 1, 2, 3 or 4 radicals R^(A);    -   p is 0, 1 or 2    -   q is 0, 1, 2 or 3;    -   R^(A) is selected from the group consisting of halogen, OH, CN,        amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        (C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,        where the aliphatic and cycloaliphatic parts of the 22        aforementioned radicals are unsubstituted, partly or completely        halogenated and where the cycloaliphatic parts of the last 4        mentioned radicals may carry 1, 2, 3, 4, 5 or 6 methyl groups,        -   it being possible that R^(A) are identical or different, it            being possible that two radicals R^(A) which are bound at            the same carbon atom may together be ═O or ═NR^(d);    -   R^(b) is selected from the group consisting of halogen, OH, CN,        amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        (C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,        where the aliphatic and cycloaliphatic parts of the 22        aforementioned radicals are unsubstituted, partly or completely        halogenated and where the cycloaliphatic parts of the last 4        mentioned radicals may carry 1, 2, 3, 4, 5 or 6 methyl groups,        -   for q=2 or 3 it being possible that R^(b) are identical or            different;    -   R^(c) is selected from the group consisting of H, OH, S(O)₂NH₂,        CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl,        C₃-C₆-cycloalkoxy, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and        (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic        parts of the 16 aforementioned radicals are unsubstituted,        partly or completely halogenated,    -   R^(d) is selected from the group consisting of H, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy,        C₂-C₆-alkynyloxy, (C₁-C₆-alkoxy)-C₁-C₆-alkyl, where the        aliphatic and cycloaliphatic parts of the 8 aforementioned        radicals are unsubstituted, partly or completely halogenated;    -   R¹ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,        C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy, C₁-C₆-alkyl, C₂-C₆-alkenyl,        C₂-C₆-alkynyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,        (C₃-C₆-cycloalkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl,        (C₁-C₆-alkyl)sulfonyl, (C₁-C₆-alkylamino)carbonyl,        di(C₁-C₆-alkyl)aminocarbonyl, (C₁-C₆-alkylamino)sulfonyl,        di(C₁-C₆-alkyl)aminosulfonyl and (C₁-C₆-alkoxy)sulfonyl, where        the aliphatic and cycloaliphatic parts of the 17 aforementioned        radicals are unsubstituted, partly or completely halogenated,        phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl, phenylaminosulfonyl,        phenylaminocarbonyl, phenyl(C₁-C₆-alkyl)aminocarbonyl,        phenylcarbonyl and phenoxycarbonyl,        -   wherein phenyl in the last 8 mentioned radicals are            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy;    -   R² is selected from the group consisting of H, OH, S(O)₂NH₂, CN,        C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy, C₁-C₆-alkyl, C₂-C₆-alkenyl,        C₂-C₆-alkynyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)carbonyl,        (C₃-C₆-cycloalkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl,        (C₁-C₆-alkyl)sulfonyl, (C₁-C₆-alkylamino)carbonyl,        di(C₁-C₆-alkyl)aminocarbonyl, (C₁-C₆-alkylamino)sulfonyl,        di(C₁-C₆-alkyl)aminosulfonyl and (C₁-C₆-alkoxy)sulfonyl, where        the aliphatic and cycloaliphatic parts of the 17 aforementioned        radicals are unsubstituted, partly or completely halogenated,        phenyl, phenylsulfonyl, phenylaminosulfonyl, phenyl-C₁-C₆ alkyl,        phenoxy, phenylaminocarbonyl, phenyl(C₁-C₆-alkyl)aminocarbonyl,        phenylcarbonyl and phenoxycarbonyl,        -   wherein phenyl in the last 8 mentioned radicals is            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy;    -   X is a radical selected from the group consisting of        -   CR³R⁴R⁵        -   phenyl, which is unsubstituted or carries 1, 2, 3, 4 or 5            radicals R^(Ar) which are identical or different;        -   NR^(3a)R^(3b),        -   OR^(3c) and        -   S(O)_(k)R^(3d) with k being 0, 1 or 2,    -    wherein    -    R³ is selected from the group consisting of H, halogen, OH, CN,        C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkyl, C₃-C₆-cycloalkyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy, C₂-C₆-alkenyloxy,        C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and        cycloaliphatic parts of the 9 aforementioned radicals are        unsubstituted, partly or completely halogenated;    -    R⁴ is selected from the group consisting of H, halogen, CN,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;    -    R⁵ is selected from the group consisting of halogen, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl, C₃-C₆-cycloalkyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkenyl and        C₁-C₆-alkoxy-C₁-C₆-alkyl, where the aliphatic and cycloaliphatic        parts of the 7 aforementioned radicals are unsubstituted, partly        or completely halogenated;    -    R⁴ and R⁵ together with the carbon atom to which they are        attached form a moiety selected from the group consisting of        carbonyl, thiocarbonyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl,        three- to six-membered saturated or partially unsaturated        heterocyclyl, and the moiety >C═CR^(x)R^(y), where R^(x) and        R^(y) are hydrogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl;    -    R^(Ar) selected from the group consisting of halogen, OH, CN,        amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkoxy)-C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,        C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        (C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,        where the aliphatic and cycloaliphatic parts of the 22        aforementioned radicals are unsubstituted, partly or completely        halogenated and where the cycloaliphatic parts of the last 4        mentioned radicals may carry 1, 2, 3, 4, 5 or 6 methyl groups,    -    R^(3a), R^(3b), R^(3c) or R^(3d) are independently of one        another are selected from the group consisting of H, CN,        S(O)₂NH₂, C₁-C₆-alkyl, C₁-C₆-alkoxy, C₂-C₆-alkenyl,        C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, (C₃-C₆-cycloalkyl)-C₁-C₆-alkyl,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,        (C₃-C₆-cycloalkyl)-carbonyl, (C₁-C₆-alkoxy)carbonyl,        (C₁-C₆-alkyl)sulfonyl, (C₁-C₆-alkylamino)carbonyl,        di(C₁-C₆-alkyl)aminocarbonyl, (C₁-C₆-alkylamino)sulfonyl,        di(C₁-C₆-alkyl)aminosulfonyl and (C₁-C₆-alkoxy)sulfonyl, where        the aliphatic and cycloaliphatic parts of the 16 aforementioned        radicals are unsubstituted, partly or completely halogenated,        -   phenyl, phenylsulfonyl, phenyl-C₁-C₆ alkyl,            phenylaminosulfonyl, phenylcarbonyl and phenoxycarbonyl,            wherein phenyl in the last 6 mentioned radicals is            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy, or    -    R^(3a), R^(3b) together with the nitrogen atom, to which they        are bound, form an N-bound, mono—or bicyclic heterocyclic        radical, which may have 1, 2, 3 or 4 further heteroatoms which        are selected from N, O and S, which is unsubstituted or        substituted by one or more identical or different substituents        selected from the group consisting of halogen, CN, NO₂,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy,        -   one of R^(3a), R^(3b) may also be OH, C₁-C₆-alkoxy,            C₃-C₆-cycloalkoxy, (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,            C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy,            (C₁-C₆-alkoxy)-C₁-C₆-alkoxy, where the aliphatic and            cycloaliphatic parts of the 6 aforementioned radicals are            unsubstituted, partly or completely halogenated, or phenoxy,            which is unsubstituted or substituted by 1, 2, 3, 4 or 5            identical or different substituents selected from the group            consisting of halogen, CN, NO₂, C₁-C₆-alkyl,            C₁-C₆-haloalkyl, C₁-C₆-alkoxy and C₁-C₆-haloalkoxy;    -   including their agriculturally acceptable salts.

In another preferred embodiment, the azines useful for the presentinvention comprise a diaminotriazine compound of formula (I)

-   -   wherein    -   A is phenyl, which is substituted by fluorine in the        ortho-position and which may additionally carry 1, 2, 3 or 4        identical or different substituents R^(A) selected from the        group consisting of halogen, OH, CN, amino, NO₂, C₁-C₆-alkyl,        C₂-C₆-alkenyl, C₂-C₆-alkynyl, (C₁-C₆-alkoxy)-C₂-C₆-alkyl,        (C₁-C₆-alkoxy)-C₂-C₆-alkenyl, (C₁-C₆-alkoxy)-C₂-C₆-alkynyl,        (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,        (C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,        C₃-C₆-cycloalkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, where the        aliphatic and cycloaliphatic parts of the 11 aforementioned        radicals are unsubstituted, partly or completely halogenated and        where the cycloaliphatic parts of the last 4 mentioned radicals        may carry 1, 2, 3, 4, 5 or 6 methyl groups;    -   R¹ is selected from the group consisting of H, OH, S(O)₂NH₂, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and        (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic        parts of the 14 aforementioned radicals are unsubstituted,        partly or completely halogenated,        -   phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl,            phenylaminosulfonyl, phenylcarbonyl and phenoxycarbonyl,        -   wherein phenyl in the last 6 mentioned radicals are            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy;    -   R² is selected from the group consisting of H, OH, S(O)₂NH₂, CN,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,        (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,        (C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        (C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and        (C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic        parts of the 14 aforementioned radicals are unsubstituted,        partly or completely halogenated,        -   phenyl, phenylsulfonyl, phenylaminosulfonyl, phenyl-C₁-C₆            alkyl, phenoxy, phenylcarbonyl and phenoxycarbonyl,        -   wherein phenyl in the last 6 mentioned radicals is            unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or            different substituents selected from the group consisting of            halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy            and C₁-C₆-haloalkoxy;    -   R³ is selected from the group consisting of C₁-C₆-alkyl,        C₂-C₆-alkenyl, C₂-C₆-alkynyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl,        (C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)carbonyl,        (C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkylamino)carbonyl and        di(C₁-C₆-alkyl)aminocarbonyl, where the aliphatic and        cycloaliphatic parts of the 9 aforementioned radicals are        unsubstituted, partly or completely halogenated,    -   R⁴ and R⁵, together with the carbon atom, to which they are        bound form a saturated 3-, 4-, 5- or 6-membered carbocyclic        radical or a saturated 3-, 4-, 5- or 6-membered heterocyclic        radical, where the carbocyclic radical and the heterocyclic        radical are unsubstituted, partly or completely halogenated or        carry from 1 to 6 C₁-C₆-alkyl groups;    -   including their agriculturally acceptable salts.

The herbicidal compounds (component A) useful for the present inventionas disclosed SUPRA may further be used in conjunction with additionalherbicides to which the crop plant is naturally tolerant or to which hasbeen made tolerant by mutagenesis as described SUPRA, or to which it isresistant via expression of one or more additional transgenes asmentioned supra. The CESA-inhibiting herbicides useful for the presentinvention are often best applied in conjunction with one or more otherherbicides to obtain control of a wider variety of undesirablevegetation. When used in conjunction with other herbicides (hereinafterreferred to a compound B), the presently claimed compounds can beformulated with the other herbicide or herbicides, tank mixed with theother herbicide or herbicides, or applied sequentially with the otherherbicide or herbicides.

The further herbicidal compound B (component B) is in particularselected from the herbicides of class b1) to b15):

-   b1) lipid biosynthesis inhibitors;-   b2) acetolactate synthase inhibitors (ALS inhibitors);-   b3) photosynthesis inhibitors;-   b4) protoporphyrinogen-IX oxidase inhibitors,-   b5) bleacher herbicides;-   b6) enolpyruvyl shikimate 3-phosphate synthase inhibitors (EPSP    inhibitors);-   b7) glutamine synthetase inhibitors;-   b8) 7,8-dihydropteroate synthase inhibitors (DHP inhibitors);-   b9) mitosis inhibitors;-   b10) inhibitors of the synthesis of very long chain fatty acids    (VLCFA inhibitors);-   b11) cellulose biosynthesis inhibitors;-   b12) decoupler herbicides;-   b13) auxinic herbicides;-   b14) auxin transport inhibitors; and-   b15) other herbicides selected from the group consisting of    bromobutide, chlorflurenol, chlorflurenol-methyl, cinmethylin,    cumyluron, dalapon, dazomet, difenzoquat, difenzoquat-metilsulfate,    dimethipin, DSMA, dymron, endothal and its salts, etobenzanid,    flamprop, flamprop-isopropyl, flamprop-methyl, flamprop-M-isopropyl,    flamprop-M-methyl, flurenol, flurenol-butyl, flurprimidol, fosamine,    fosamine-ammonium, indanofan, indaziflam, maleic hydrazide,    mefluidide, metam, methiozolin (CAS 403640-27-7), methyl azide,    methyl bromide, methyl-dymron, methyl iodide, MSMA, oleic acid,    oxaziclomefone, pelargonic acid, pyributicarb, quinoclamine,    triaziflam, tridiphane and    6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (CAS    499223-49-3) and its salts and esters;    -   including their agriculturally acceptable salts or derivatives        such as ethers, esters or amides.

Preference is given to those compositions according to the presentinvention comprising at least one herbicide B selected from herbicidesof class b1, b6, b9, b10 and b11

Examples of herbicides B which can be used in combination with thecompounds of formula (I) according to the present invention are:

b1) from the group of the lipid biosynthesis inhibitors:

ACC-herbicides such as alloxydim, alloxydim-sodium, butroxydim,clethodim, clodinafop, clodinafop-propargyl, cycloxydim, cyhalofop,cyhalofop-butyl, diclofop, diclofop-methyl, fenoxaprop,fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fluazifop,fluazifop-butyl, fluazifop-P, fluazifop-P-butyl, haloxyfop,haloxyfop-methyl, haloxyfop-P, haloxyfop-P-methyl, metamifop, pinoxaden,profoxydim, propaquizafop, quizalofop, quizalofop-ethyl,quizalofop-tefuryl, quizalofop-P, quizalofop-P-ethyl,quizalofop-P-tefuryl, sethoxydim, tepraloxydim, tralkoxydim,4-(4′-Chloro-4-cyclopropyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5-hydroxy-2,2,6,6-tetramethyl-2H-pyran-3(6H)-one(CAS 1312337-72-6);4-(2′,4′-Dichloro-4-cyclopropyl[1,1′-biphenyl]-3-yl)-5-hydroxy-2,2,6,6-tetramethyl-2H-pyran-3(6H)-one(CAS 1312337-45-3);4-(4′-Chloro-4-ethyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5-hydroxy-2,2,6,6-tetramethyl-2H-pyran-3(6H)-one(CAS 1033757-93-5);4-(2′,4′-Dichloro-4-ethyl[1,1′-biphenyl]-3-yl)-2,2,6,6-tetramethyl-2H-pyran-3,5(4H,6H)-dione(CAS 1312340-84-3);5-(Acetyloxy)-4-(4′-chloro-4-cyclopropyl-2′-fluoro[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one(CAS 1312337-48-6);5-(Acetyloxy)-4-(2′,4′-dichloro-4-cyclopropyl-[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one;5-(Acetyloxy)-4-(4′-chloro-4-ethyl-2′-fluoro[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one(CAS 1312340-82-1);5-(Acetyloxy)-4-(2′,4′-dichloro-4-ethyl[1,1′-biphenyl]-3-yl)-3,6-dihydro-2,2,6,6-tetramethyl-2H-pyran-3-one(CAS 1033760-55-2);4-(4′-Chloro-4-cyclopropyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonicacid methyl ester (CAS 1312337-51-1);4-(2″,4′-Dichloro-4-cyclopropyl-[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonic acid methyl ester;4-(4′-Chloro-4-ethyl-2′-fluoro[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonicacid methyl ester (CAS 1312340-83-2);4-(2′,4′-Dichloro-4-ethyl[1,1′-biphenyl]-3-yl)-5,6-dihydro-2,2,6,6-tetramethyl-5-oxo-2H-pyran-3-ylcarbonicacid methyl ester (CAS 1033760-58-5); and non ACC herbicides such asbenfuresate, butylate, cycloate, dalapon, dimepiperate, EPTC, esprocarb,ethofumesate, flupropanate, molinate, orbencarb, pebulate, prosulfocarb,TCA, thiobencarb, tiocarbazil, triallate and vernolate;b2) from the group of the ALS inhibitors:sulfonylureas such as amidosulfuron, azimsulfuron, bensulfuron,bensulfuron-methyl, chlorimuron, chlorimuron-ethyl, chlorsulfuron,cinosulfuron, cyclosulfamuron, ethametsulfuron, ethametsulfuron-methyl,ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron,flupyrsulfuron-methyl-sodium, foramsulfuron, halosulfuron,halosulfuron-methyl, imazosulfuron, iodosulfuron,iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium,mesosulfuron, metazosulfuron, metsulfuron, metsulfuron-methyl,nicosulfuron, orthosulfamuron, oxasulfuron, primisulfuron,primisulfuron-methyl, propyrisulfuron, prosulfuron, pyrazosulfuron,pyrazosulfuron-ethyl, rimsulfuron, sulfometuron, sulfometuron-methyl,sulfosulfuron, thifensulfuron, thifensulfuron-methyl, triasulfuron,tribenuron, tribenuron-methyl, trifloxysulfuron, triflusulfuron,triflusulfuron-methyl and tritosulfuron,imidazolinones such as imazamethabenz, imazamethabenz-methyl, imazamox,imazapic, imazapyr, imazaquin and imazethapyr, triazolopyrimidineherbicides and sulfonanilides such as cloransulam, cloransulam-methyl,diclosulam, flumetsulam, florasulam, metosulam, penoxsulam, pyrimisulfanand pyroxsulam,pyrimidinylbenzoates such as bispyribac, bispyribac-sodium,pyribenzoxim, pyriftalid, pyriminobac, pyriminobac-methyl, pyrithiobac,pyrithiobac-sodium,4-[[[2-[(4,6-dimethoxy-2-pyrimidinyl)oxy]phenyl]methyl]amino]-benzoicacid-1-methylethyl ester (CAS 420138-41-6),4-[[[2-[(4,6-dimethoxy-2-pyrimidinyl)oxy]phenyl]methyl]amino]-benzoicacid propyl ester (CAS 420138-40-5),N-(4-bromophenyl)-2-[(4,6-dimethoxy-2-pyrimidinyl)oxy]benzenemethanamine(CAS 420138-01-8), sulfonylaminocarbonyl-triazolinone herbicides such asflucarbazone, flucarbazone-sodium, propoxycarbazone,propoxycarbazone-sodium, thiencarbazone and thiencarbazone-methyl; andtriafamone;among these, a preferred embodiment of the invention relates to thosecompositions comprising at least one imidazolinone herbicide;b3) from the group of the photosynthesis inhibitors:amicarbazone, inhibitors of the photosystem II, e.g. triazineherbicides, including of chlorotriazine, triazinones, triazindiones,methylthiotriazines and pyridazinones such as ametryn, atrazine,chloridazone, cyanazine, desmetryn, dimethametryn, hexazinone,metribuzin, prometon, prometryn, propazine, simazine, simetryn,terbumeton, terbuthylazin, terbutryn and trietazin, aryl urea such aschlorobromuron, chlorotoluron, chloroxuron, dimefuron, diuron,fluometuron, isoproturon, isouron, linuron, metamitron,methabenzthiazuron, metobenzuron, metoxuron, monolinuron, neburon,siduron, tebuthiuron and thiadiazuron, phenyl carbamates such asdesmedipham, karbutilat, phenmedipham, phenmedipham-ethyl, nitrileherbicides such as bromofenoxim, bromoxynil and its salts and esters,ioxynil and its salts and esters, uraciles such as bromacil, lenacil andterbacil, and bentazon and bentazon-sodium, pyridate, pyridafol,pentanochlor and propanil and inhibitors of the photosystem I such asdiquat, diquat-dibromide, paraquat, paraquat-dichloride andparaquat-dimetilsulfate. Among these, a preferred embodiment of theinvention relates to those compositions comprising at least one arylurea herbicide. Among these, likewise a preferred embodiment of theinvention relates to those compositions comprising at least one triazineherbicide. Among these, likewise a preferred embodiment of the inventionrelates to those compositions comprising at least one nitrile herbicide;b4) from the group of the protoporphyrinogen-IX oxidase inhibitors:acifluorfen, acifluorfen-sodium, azafenidin, bencarbazone,benzfendizone, bifenox, butafenacil, carfentrazone, carfentrazone-ethyl,chlomethoxyfen, cinidon-ethyl, fluazolate, flufenpyr, flufenpyr-ethyl,flumiclorac, flumiclorac-pentyl, flumioxazin, fluoroglycofen,fluoroglycofen-ethyl, fluthiacet, fluthiacet-methyl, fomesafen,halosafen, lactofen, oxadiargyl, oxadiazon, oxyfluorfen, pentoxazone,profluazol, pyraclonil, pyraflufen, pyraflufen-ethyl, saflufenacil,sulfentrazone, thidiazimin, tiafenacil, ethyl[3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetate(CAS 353292-31-6; S-3100),N-ethyl-3-(2,6-dichloro-4-trifluoromethylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 452098-92-9),N-tetrahydrofurfuryl-3-(2,6-dichloro-4-trifluoromethylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 915396-43-9),N-ethyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 452099-05-7),N-tetrahydrofurfuryl-3-(2-chloro-6-fluoro-4-trifluoromethylphenoxy)-5-methyl-1H-pyrazole-1-carboxamide(CAS 452100-03-7),3-[7-fluoro-3-oxo-4-(prop-2-ynyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-1,5-dimethyl-6-thioxo-[1,3,5]triazinan-2,4-dione,1,5-dimethyl-6-thioxo-3-(2,2,7-trifluoro-3-oxo-4-(prop-2-ynyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1,3,5-triazinane-2,4-dione(CAS 1258836-72-4),2-(2,2,7-Trifluoro-3-oxo-4-prop-2-ynyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,5,6,7-tetrahydro-isoindole-1,3-dione,1-Methyl-6-trifluoromethyl-3-(2,2,7-trifluoro-3-oxo-4-prop-2-ynyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-1H-pyrimidine-2,4-dione,methyl(E)-4-[2-chloro-5-[4-chloro-5-(difluoromethoxy)-1H-methyl-pyrazol-3-yl]-4-fluoro-phenoxy]-3-methoxy-but-2-enoate[CAS 948893-00-3], and3-[7-Chloro-5-fluoro-2-(trifluoromethyl)-1H-benzimidazol-4-yl]-1-methyl-6-(trifluoromethyl)-1H-pyrimidine-2,4-dione(CAS 212754-02-4);b5) from the group of the bleacher herbicides:PDS inhibitors: beflubutamid, diflufenican, fluridone, flurochloridone,flurtamone, norflurazon, picolinafen, and4-(3-trifluoromethylphenoxy)-2-(4-trifluoromethylphenyl)-pyrimidine (CAS180608-33-7), HPPD inhibitors: benzobicyclon, benzofenap, clomazone,fenquintrione, isoxaflutole, mesotrione, pyrasulfotole, pyrazolynate,pyrazoxyfen, sulcotrione, tefuryltrione, tembotrione, topramezone andbicyclopyrone, bleacher, unknown target: aclonifen, amitrole andflumeturon;b6) from the group of the EPSP synthase inhibitors:glyphosate, glyphosate-isopropylammonium, glyposate-potassium andglyphosate-trimesium (sulfosate);b7) from the group of the glutamine synthase inhibitors:bilanaphos (bialaphos), bilanaphos-sodium, glufosinate, glufosinate-Pand glufosinate-ammonium;b8) from the group of the DHP synthase inhibitors:asulam;b9) from the group of the mitosis inhibitors:compounds of group K1: dinitroanilines such as benfluralin, butralin,dinitramine, ethalfluralin, fluchloralin, oryzalin, pendimethalin,prodiamine and trifluralin, phosphoramidates such as amiprophos,amiprophos-methyl, and butamiphos, benzoic acid herbicides such aschlorthal, chlorthal-dimethyl, pyridines such as dithiopyr andthiazopyr, benzamides such as propyzamide and tebutam; compounds ofgroup K2: chlorpropham, propham and carbetamide, among these, compoundsof group K1, in particular dinitroanilines are preferred;b10) from the group of the VLCFA inhibitors:chloroacetamides such as acetochlor, alachlor, butachlor, dimethachlor,dimethenamid, dimethenamid-P, metazachlor, metolachlor, metolachlor-S,pethoxamid, pretilachlor, propachlor, propisochlor and thenylchlor,oxyacetanilides such as flufenacet and mefenacet, acetanilides such asdiphenamid, naproanilide, napropamide and napropamide-M, tetrazolinonessuch fentrazamide, and other herbicides such as anilofos, cafenstrole,fenoxasulfone, ipfencarbazone, piperophos, pyroxasulfone and isoxazolinecompounds of the formulae II.1, II.2, II.3, II.4, II.5, II.6, II.7, II.8and II.9

the isoxazoline compounds of the formula (I)I are known in the art, e.g.from WO 2006/024820, WO 2006/037945, WO 2007/071900 and WO 2007/096576;among the VLCFA inhibitors, preference is given to chloroacetamides andoxyacetamides;b11) from the group of the cellulose biosynthesis inhibitors:chlorthiamid, dichlobenil, flupoxam, isoxaben and1-Cyclohexyl-5-pentafluorphenyloxy-1⁴-[1,2,4,6]thiatriazin-3-ylamine;b12) from the group of the decoupler herbicides:dinoseb, dinoterb and DNOC and its salts;b13) from the group of the auxinic herbicides:2,4-D and its salts and esters such as clacyfos, 2,4-DB and its saltsand esters, aminocyclopyrachlor and its salts and esters, aminopyralidand its salts such as aminopyralid-dimethylammonium,aminopyralid-tris(2-hydroxypropyl)ammonium and its esters, benazolin,benazolin-ethyl, chloramben and its salts and esters, clomeprop,clopyralid and its salts and esters, dicamba and its salts and esters,dichlorprop and its salts and esters, dichlorprop-P and its salts andesters, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, halauxifenand its salts and esters (CAS 943832-60-8); MCPA and its salts andesters, MCPA-thioethyl, MCPB and its salts and esters, mecoprop and itssalts and esters, mecoprop-P and its salts and esters, picloram and itssalts and esters, quinclorac, quinmerac, TBA (2,3,6) and its salts andesters and triclopyr and its salts and esters;b14) from the group of the auxin transport inhibitors: diflufenzopyr,diflufenzopyr-sodium, naptalam and naptalam-sodium;b15) from the group of the other herbicides: bromobutide, chlorflurenol,chlorflurenol-methyl, cinmethylin, cumyluron, cyclopyrimorate (CAS499223-49-3) and its salts and esters, dalapon, dazomet, difenzoquat,difenzoquat-metilsulfate, dimethipin, DSMA, dymron, endothal and itssalts, etobenzanid, flamprop, flamprop-isopropyl, flamprop-methyl,flamprop-M-isopropyl, flamprop-M-methyl, flurenol, flurenol-butyl,flurprimidol, fosamine, fosamine-ammonium, indanofan, indaziflam, maleichydrazide, mefluidide, metam, methiozolin (CAS 403640-27-7), methylazide, methyl bromide, methyl-dymron, methyl iodide, MSMA, oleic acid,oxaziclomefone, pelargonic acid, pyributicarb, quinoclamine, triaziflamand tridiphane.

Active compounds B and C having a carboxyl group can be employed in theform of the acid, in the form of an agriculturally suitable salt asmentioned above or else in the form of an agriculturally acceptablederivative in the compositions according to the invention.

In the case of dicamba, suitable salts include those, where thecounterion is an agriculturally acceptable cation. For example, suitablesalts of dicamba are dicamba-sodium, dicamba-potassium,dicamba-methylammonium, dicamba-dimethylammonium,dicamba-isopropylammonium, dicamba-diglycolamine, dicamba-olamine,dicamba-diolamine, dicamba-trolamine,dicamba-N,N-bis-(3-aminopropyl)methylamine anddicamba-diethylenetriamine. Examples of a suitable ester aredicamba-methyl and dicamba-butotyl.

Suitable salts of 2,4-D are 2,4-D-ammonium, 2,4-D-dimethylammonium,2,4-D-diethylammonium, 2,4-D-diethanolammonium (2,4-D-diolamine),2,4-D-triethanol-ammonium, 2,4-D-isopropylammonium,2,4-D-triisopropanolammonium, 2,4-D-heptylammonium,2,4-D-dodecylammonium, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium,2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-tris(isopropyl)ammonium,2,4-D-trolamine, 2,4-D-lithium, 2,4-D-sodium. Examples of suitableesters of 2,4-D are 2,4-D-butotyl, 2,4-D-2-butoxypropyl,2,4-D-3-butoxypropyl, 2,4-D-butyl, 2,4-D-ethyl, 2,4-D-ethylhexyl,2,4-D-isobutyl, 2,4-D-isooctyl, 2,4-D-isopropyl, 2,4-D-meptyl,2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-propyl, 2,4-D-tefuryl andclacyfos.

Suitable salts of 2,4-DB are for example 2,4-DB-sodium, 2,4-DB-potassiumand 2,4-DB-dimethylammonium. Suitable esters of 2,4-DB are for example2,4-DB-butyl and 2,4-DB-isoctyl.

Suitable salts of dichlorprop are for example dichlorprop-sodium,dichlorprop-potassium and dichlorprop-dimethylammonium. Examples ofsuitable esters of dichlorprop are dichlorprop-butotyl anddichlorprop-isoctyl.

Suitable salts and esters of MCPA include MCPA-butotyl, MCPA-butyl,MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-thioethyl,MCPA-2-ethylhexyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,MCPA-isopropylammonium, MCPA-methyl, MCPA-olamine, MCPA-potassium,MCPA-sodium and MCPA-trolamine.

A suitable salt of MCPB is MCPB sodium. A suitable ester of MCPB isMCPB-ethyl.

Suitable salts of clopyralid are clopyralid-potassium,clopyralid-olamine and clopyralid-tris-(2-hydroxypropyl)ammonium.Example of suitable esters of clopyralid is clopyralid-methyl.

Examples of a suitable ester of fluroxypyr are fluroxypyr-meptyl andfluroxypyr-2-butoxy-1-methylethyl, wherein fluroxypyr-meptyl ispreferred.

Suitable salts of picloram are picloram-dimethylammonium,picloram-potassium, picloram-triisopropanolammonium,picloram-triisopropylammonium and picloram-trolamine. A suitable esterof picloram is picloram-isoctyl.

A suitable salt of triclopyr is triclopyr-triethylammonium. Suitableesters of triclopyr are for example triclopyr-ethyl andtriclopyr-butotyl.

Suitable salts and esters of chloramben include chloramben-ammonium,chloramben-diolamine, chloramben-methyl, chloramben-methylammonium andchloramben-sodium. Suitable salts and esters of 2,3,6-TBA include2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium and2,3,6-TBA-sodium.

Suitable salts and esters of aminopyralid includeaminopyralid-potassium, aminopyralid-dimethylammonium, andaminopyralid-tris(2-hydroxypropyl)ammonium.

Suitable salts of glyphosate are for example glyphosate-ammonium,glyphosate-diammonium, glyphoste-dimethylammonium,glyphosate-isopropylammonium, glyphosate-potassium, glyphosate-sodium,glyphosate-trimesium as well as the ethanolamine and diethanolaminesalts, preferably glyphosate-diammonium, glyphosate-isopropylammoniumand glyphosate-trimesium (sulfosate).

A suitable salt of glufosinate is for example glufosinate-ammonium.

A suitable salt of glufosinate-P is for example glufosinate-P-ammonium.

Suitable salts and esters of bromoxynil are for examplebromoxynil-butyrate, bromoxynil-heptanoate, bromoxynil-octanoate,bromoxynil-potassium and bromoxynil-sodium.

Suitable salts and esters of ioxonil are for example ioxonil-octanoate,ioxonil-potassium and ioxonil-sodium.

Suitable salts and esters of mecoprop include mecoprop-butotyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-2-ethylhexyl, mecoprop-isoctyl, mecoprop-methyl,mecoprop-potassium, mecoprop-sodium and mecoprop-trolamine.

Suitable salts of mecoprop-P are for example mecoprop-P-butotyl,mecoprop-P-dimethylammonium, mecoprop-P-2-ethylhexyl,mecoprop-P-isobutyl, mecoprop-P-potassium and mecoprop-P-sodium.

A suitable salt of diflufenzopyr is for example diflufenzopyr-sodium.

A suitable salt of naptalam is for example naptalam-sodium.

Suitable salts and esters of aminocyclopyrachlor are for exampleaminocyclopyrachlor-dimethylammonium, aminocyclopyrachlor-methyl,aminocyclopyrachlor-triisopropanolammonium, aminocyclopyrachlor-sodiumand aminocyclopyrachlor-potassium.

A suitable salt of quinclorac is for examplequinclorac-dimethylammonium.

A suitable salt of quinmerac is for example quinclorac-dimethylammonium.

A suitable salt of imazamox is for example imazamox-ammonium.

Suitable salts of imazapic are for example imazapic-ammonium andimazapic-isopropylammonium.

Suitable salts of imazapyr are for example imazapyr-ammonium andimazapyr-isopropylammonium.

A suitable salt of imazaquin is for example imazaquin-ammonium.

Suitable salts of imazethapyr are for example imazethapyr-ammonium andimazethapyr-isopropylammonium.

A suitable salt of topramezone is for example topramezone-sodium.

Particularly preferred herbicidal compounds B are the herbicides B asdefined above; in particular the herbicides B.1-B.189 listed below intable B:

TABLE B Herbicide B B.1 clethodim B.2 clodinafop-propargyl B.3cycloxydim B.4 cyhalofop-butyl B.5 fenoxaprop-ethyl B.6fenoxaprop-P-ethyl B.7 metamifop B.8 pinoxaden B.9 profoxydim B.10sethoxydim B.11 tepraloxydim B.12 tralkoxydim B.13 esprocarb B.14ethofumesate B.15 molinate B.16 prosulfocarb B.17 thiobencarb B.18triallate B.19 bensulfuron-methyl B.20 bispyribac-sodium B.21cloransulam-methyl B.22 chlorsulfuron B.23 clorimuron B.24cyclosulfamuron B.25 diclosulam B.26 florasulam B.27 flumetsulam B.28flupyrsulfuron-methyl-sodium B.29 foramsulfuron B.30 imazamox B.31imazamox-ammonium B.32 imazapic B.33 imazapic-ammonium B.34imazapic-isopropylammonium B.35 imazapyr B.36 imazapyr-ammonium B.37imazapyr-isopropylammonium B.38 imazaquin B.39 imazaquin-ammonium B.40imazethapyr B.41 imazethapyr-ammonium B.42 imazethapyr-isopropylammonium B.43 imazosulfuron B.44 iodosulfuron-methyl-sodiumB.45 iofensulfuron B.46 iofensulfuron-sodium B.47 mesosulfuron-methylB.48 metazosulfuron B.49 metsulfuron-methyl B.50 metosulam B.51nicosulfuron B.52 penoxsulam B.53 propoxycarbazon-sodium B.54pyrazosulfuron-ethyl B.55 pyribenzoxim B.56 pyriftalid B.57 pyroxsulamB.58 propyrisulfuron B.59 rimsulfuron B.60 sulfosulfuron B.61thiencarbazone-methyl B.62 thifensulfuron-methyl B.63 tribenuron-methylB.64 tritosulfuron B.65 triafamone B.66 ametryne B.67 atrazine B.68bentazon B.69 bromoxynil B.70 bromoxynil-octanoate B.71bromoxynil-heptanoate B.72 bromoxynil-potassium B.73 diuron B.74fluometuron B.75 hexazinone B.76 isoproturon B.77 linuron B.78metamitron B.79 metribuzin B.80 propanil B.81 simazin B.82terbuthylazine B.83 terbutryn B.84 paraquat-dichloride B.85 acifluorfenB.86 butafenacil B.87 carfentrazone-ethyl B.88 flumioxazin B.89fomesafen B.90 oxadiargyl B.91 oxyfluorfen B.92 saflufenacil B.93sulfentrazone B.94 ethyl [3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl- 2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-3-yl)phenoxy]-2- pyridyloxy]acetate (CAS 353292-31-6) B.951,5-dimethyl-6-thioxo-3-(2,2,7- trifluoro-3-oxo-4-(prop-2-ynyl)-3,4-dihydro-2H-benzo[b][1,4]- oxazin-6-yl)-1,3,5-triazinane- 2,4-dione(CAS 1258836-72- 4) B.96 benzobicyclon B.97 clomazone B.98 diflufenicanB.99 flurochloridone B.100 isoxaflutole B.101 mesotrione B.102norflurazone B.103 picolinafen B.104 sulcotrione B.105 tefuryltrioneB.106 tembotrione B.107 topramezone B.108 topramezone-sodium B.109bicyclopyrone B.110 amitrole B.111 fluometuron B.112 fenquintrione B.113glyphosate B.114 glyphosate-ammonium B.115 glyphosate- dimethylammoniumB.116 glyphosate- isopropylammonium B.117 glyphosate-trimesium(sulfosate) B.118 glyphosate-potassium B.119 glufosinate B.120glufosinate-ammonium B.121 glufosinate-P B.122 glufosinate-P-ammoniumB.123 pendimethalin B.124 trifluralin B.125 acetochlor B.126 butachlorB.127 cafenstrole B.128 dimethenamid-P B.129 fentrazamide B.130flufenacet B.131 mefenacet B.132 metazachlor B.133 metolachlor B.134S-metolachlor B.135 pretilachlor B.136 fenoxasulfone B.137 isoxabenB.138 ipfencarbazone B.139 pyroxasulfone B.140 2,4-D B.1412,4-D-isobutyl B.142 2,4-D-dimethylammonium B.143 2,4-D-N,N,N-trimethylethanolammonium B.144 aminopyralid B.145 aminopyralid-methylB.146 aminopyralid-dimethyl- ammonium B.147 aminopyralid-tris(2-hydroxypropyl)ammonium B.148 clopyralid B.149 clopyralid-methyl B.150clopyralid-olamine B.151 dicamba B.152 dicamba-butotyl B.153dicamba-diglycolamine B.154 dicamba-dimethylammonium B.155dicamba-diolamine B.156 dicamba-isopropylammonium B.157dicamba-potassium B.158 dicamba-sodium B.159 dicamba-trolamine B.160dicamba-N,N-bis-(3- aminopropyl)methylamine B.161dicamba-diethylenetriamine B.162 fluroxypyr B.163 fluroxypyr-meptylB.164 MCPA B.165 MCPA-2-ethylhexyl B.166 MCPA-dimethylammonium B.167quinclorac B.168 quinclorac-dimethylammonium B.169 quinmerac B.170quinmerac- dimethylammonium B.171 aminocyclopyrachlor B.172aminocyclopyrachlor- potassium B.173 aminocyclopyrachlor-methyl B.174diflufenzopyr B.175 diflufenzopyr-sodium B.176 dymron B.177 indanofanB.178 indaziflam B.179 oxaziclomefone B.180 triaziflam B.181 II.1 B.182II.2 B.183 II.3 B.184 II.4 B.185 II.5 B.186 II.6 B.187 II.7 B.188 II.8B.189 II.9

Moreover, it may be useful to apply the compounds of formula (I) incombination with safeners and optionally with one or more furtherheribicides. Safeners are chemical compounds which prevent or reducedamage on useful plants without having a major impact on the herbicidalaction of the compounds of the formula (I) towards unwanted plants. Theycan be applied either before sowings (e.g. on seed treatments, shoots orseedlings) or in the pre-emergence application or post-emergenceapplication of the useful plant. The safeners and the compounds offormula (I) and optionally the herbicides B can be appliedsimultaneously or in succession.

Suitable safeners are e.g. (quinolin-8-oxy)acetic acids,1-phenyl-5-haloalkyl-1H-1,2,4-triazol-3-carboxylic acids,1-phenyl-4,5-dihydro-5-alkyl-1H-pyrazol-3,5-dicarboxylic acids,4,5-dihydro-5,5-diary)-3-isoxazol carboxylic acids, dichloroacetamides,alpha-oximinophenylacetonitriles, acetophenonoximes,4,6-dihalo-2-phenylpyrimidines,N-[[4-(aminocarbonyl)phenyl]sulfonyl]-2-benzoic amides, 1,8-naphthalicanhydride, 2-halo-4-(haloalkyl)-5-thiazol carboxylic acids,phosphorthiolates and N-alkyl-O-phenylcarbamates and theiragriculturally acceptable salts and their agriculturally acceptablederivatives such amides, esters, and thioesters, provided they have anacid group.

Examples of preferred safeners C are benoxacor, cloquintocet,cyometrinil, cyprosulfamide, dichlormid, dicyclonon, dietholate,fenchlorazole, fenclorim, flurazole, fluxofenim, furilazole, isoxadifen,mefenpyr, mephenate, naphthalic anhydride, oxabetrinil,4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (MON4660, CAS71526-07-3), 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine(R-29148, CAS 52836-31-4) andN-(2-Methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide(CAS 129531-12-0).

Particularly preferred safeners C are the following compounds C.1 toC.17

C.1 benoxacor C.2 cloquintocet C.3 cloquintocet-mexyl C.4 cyprosulfamideC.5 dichlormid C.6 fenchlorazole C.7 fenchlorazole-ethyl C.8 fenclorimC.9 furilazole C.10 isoxadifen C.11 isoxadifen-ethyl C.12 mefenpyr C.13mefenpyr-diethyl C.14 naphtalic acid anhydride C.154-(dichloroacetyl)-1-oxa-4- C.16 2,2,5-trimethyl-3-(dichloro-azaspiro[4.5]decane acetyl)-1,3-oxazolidine C.17 N-(2-Methoxybenzoyl)-4-[(methylamino- carbonyl)amino]ben- zenesulfonamide

The active compounds B of groups b1) to b15) and the safener compounds Care known herbicides and safeners, see, for example, The Compendium ofPesticide Common Names (http://www.alanwood.net/pesticides/); FarmChemicals Handbook 2000 volume 86, Meister Publishing Company, 2000; B.Hock, C. Fedtke, R. R. Schmidt, Herbizide [Herbicides], Georg ThiemeVerlag, Stuttgart 1995; W. H. Ahrens, Herbicide Handbook, 7th edition,Weed Science Society of America, 1994; and K. K. Hatzios, HerbicideHandbook, Supplement for the 7th edition, Weed Science Society ofAmerica, 1998. 2,2,5-Trimethyl-3-(dichloroacetyl)-1,3-oxazolidine [CASNo. 52836-31-4] is also referred to as R-29148.4-(Dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane [CAS No. 71526-07-3] isalso referred to as AD-67 and MON 4660.

The assignment of the active compounds to the respective mechanisms ofaction is based on current knowledge. If several mechanisms of actionapply to one active compound, this substance was only assigned to onemechanism of action.

It is generally preferred to use the compounds of the invention incombination with herbicides that are selective for the crop beingtreated and which complement the spectrum of weeds controlled by thesecompounds at the application rate employed. It is further generallypreferred to apply the compounds of the invention and othercomplementary herbicides at the same time, either as a combinationformulation or as a tank mix.

In another embodiment, the present invention refers to a method foridentifying a CESA-inhibiting herbicide by using a wildtype or mutatedCESA encoded by a nucleic acid which comprises the nucleotide sequenceof SEQ ID NO: 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, or 77, ora variant or derivative thereof.

Said method comprises the steps of:

-   a) generating a transgenic cell or plant comprising a nucleic acid    encoding a wildtype or mutated CESA, wherein the wildtype or mutated    CESA is expressed;-   b) applying a CESA-inhibiting herbicide to the transgenic cell or    plant of a) and to a control cell or plant of the same variety;-   c) determining the growth or the viability of the transgenic cell or    plant and the control cell or plant after application of said    CESA-inhibiting herbicide, and-   d) selecting “CESA-inhibiting herbicides” which confer reduced    growth to the control cell or plant as compared to the growth of the    transgenic cell or plant.

As described above, the present invention teaches compositions andmethods for increasing the CESA-inhibiting tolerance of a crop plant orseed as compared to a wild-type variety of the plant or seed. In apreferred embodiment, the CESA-inhibiting tolerance of a crop plant orseed is increased such that the plant or seed can withstand aCESA-inhibiting herbicide application of preferably approximately 1-1000g ai ha⁻¹, more preferably 1-200 g ai ha⁻¹, even more preferably 5-150 gai ha⁻¹, and most preferably 10-100 g ai ha⁻¹. As used herein, to“withstand” a CESA-inhibiting herbicide application means that the plantis either not killed or only moderately injured by such application. Itwill be understood by the person skilled in the art that the applicationrates may vary, depending on the environmental conditions such astemperature or humidity, and depending on the chosen kind of herbicide(active ingredient ai).

Pre- and/or Post-emergent weed control methods useful in variousembodiments hereof utilize about >0.3× application rates ofCESA-inhibiting herbicides; in some embodiments, this can be about, forexample, >0.3×, >0.4×, >0.5×, >0.6×, >0.7×, >0.8×, >0.9×, or >1× ofCESA-inhibiting herbicides. In one embodiment, CESA-inhibitingherbicides-tolerant plants of the present invention have tolerance to apre- and/or post-emergant application of a CESA-inhibiting herbicides atan amount of about 25 to about 500 g ai/ha. In some embodiments, whereinthe CESA-inhibiting herbicides-tolerant plant is a dicot (e.g., soy,cotton), the pre- and/or post-emergant application of theCESA-inhibiting herbicides is at an amount of about 25-250 g ai/ha. Inanother embodiment, wherein the CESA-inhibiting herbicides-tolerantplant is a monocot (e.g., maize, rice, sorghum), the pre- and/orpost-emergant application of the CESA-inhibiting herbicides is at anamount of about 50-500 g ai/ha. In other embodiments, wherein theCESA-inhibiting herbicides-tolerant plant is a Brassica (e.g., canola),the pre- and/or post-emergant application of the CESA-inhibitingherbicides is at an amount of about 25-200 g ai/ha. In pre- and/orpost-emergent weed control methods hereof, in some embodiments, themethod can utilize CESA-inhibiting herbicides application rates atpre-emergent and/or about 7 to 10 days post-emergent. In anotherembodiment, the application rate can exceed 8×CESA-inhibitingherbicides; in some embodiments, the rate can be up to 4×CESA-inhibitingherbicides, though more typically it will be about 2.5× or less, orabout 2× or less, or about 1× or less.

Furthermore, the present invention provides methods that involve the useof at least one CESA-inhibiting herbicide, optionally in combinationwith one or more herbicidal compounds B, and, optionally, a safener C,as described in detail supra.

In these methods, the CESA-inhibiting herbicide can be applied by anymethod known in the art including, but not limited to, seed treatment,soil treatment, and foliar treatment. Prior to application, theCESA-inhibiting herbicide can be converted into the customaryformulations, for example solutions, emulsions, suspensions, dusts,powders, pastes and granules. The use form depends on the particularintended purpose; in each case, it should ensure a fine and evendistribution of the compound according to the invention.

By providing plants having increased tolerance to CESA-inhibitingherbicide, a wide variety of formulations can be employed for protectingplants from weeds, so as to enhance plant growth and reduce competitionfor nutrients. A CESA-inhibiting herbicide can be used by itself forpre-emergence, post-emergence, pre-planting, and at-planting control ofweeds in areas surrounding the crop plants described herein, or aCESA-inhibiting herbicide formulation can be used that contains otheradditives. The CESA-inhibiting herbicide can also be used as a seedtreatment. Additives found in a CESA-inhibiting herbicide formulationinclude other herbicides, detergents, adjuvants, spreading agents,sticking agents, stabilizing agents, or the like. The CESA-inhibitingherbicide formulation can be a wet or dry preparation and can include,but is not limited to, flowable powders, emulsifiable concentrates, andliquid concentrates. The CESA-inhibiting herbicide and herbicideformulations can be applied in accordance with conventional methods, forexample, by spraying, irrigation, dusting, or the like.

Suitable formulations are described in detail in PCT/EP2009/063387 andPCT/EP2009/063386, which are incorporated herein by reference.

As disclosed herein, the CESA nucleic acids of the invention find use inenhancing the CBI herbicide tolerance of plants that comprise in theirgenomes a gene encoding a herbicide-tolerant wildtype or mutated CESAprotein. Such a gene may be an endogenous gene or a transgene, asdescribed above. Additionally, in certain embodiments, the nucleic acidsof the present invention can be stacked with any combination ofpolynucleotide sequences of interest in order to create plants with adesired phenotype. For example, the nucleic acids of the presentinvention may be stacked with any other polynucleotides encodingpolypeptides having pesticidal and/or insecticidal activity, such as,for example, the Bacillus thuringiensis toxin proteins (described inU.S. Pat. Nos. 5,366,892; 5,747,450; 5,737,514; 5,723,756; 5,593,881;and Geiser et al (1986) Gene 48: 109),5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), Glyphosate acetyltransferase (GAT), cytochrome P450 monooxygenase, phosphinothricinacetyltransferase (PAT), Acetohydroxyacid synthase (AHAS; EC 4.1.3.18,also known as acetolactate synthase or ALS), hydroxyphenyl pyruvatedioxygenase (HPPD), Phytoene desaturase (PD), Protoporphyrinogen oxidase(PPO) and dicamba degrading enzymes as disclosed in WO 02/068607, orphenoxyaceticacid- and phenoxypropionicacid-derivative degrading enzymesas disclosed in WO 2008141154 or WO 2005107437. The combinationsgenerated can also include multiple copies of any one of thepolynucleotides of interest.

Consequently, Herbicide-tolerant plants of the invention can be used inconjunction with an herbicide to which they are tolerant. Herbicides canbe applied to the plants of the invention using any techniques known tothose skilled in the art. Herbicides can be applied at any point in theplant cultivation process. For example, herbicides can be appliedpre-planting, at planting, pre-emergence, post-emergence or combinationsthereof. Herbicides may be applied to seeds and dried to form a layer onthe seeds.

In some embodiments, seeds are treated with a safener, followed by apost-emergent application of a CESA-inhibiting herbicides. In oneembodiment, the post-emergent application of the CESA-inhibitingherbicides is about 7 to 10 days following planting of safener-treatedseeds. In some embodiments, the safener is cloquintocet, dichlormid,fluxofenim, or combinations thereof.

Methods of controlling weeds or undesired vegetation

In other aspects, the present invention provides a method forcontrolling weeds at a locus for growth of a plant or plant partthereof, the method comprising: applying a composition comprising aCESA-inhibiting herbicides to the locus.

In some aspects, the present invention provides a method for controllingweeds at a locus for growth of a plant, the method comprising: applyingan herbicide composition comprising CESA-inhibiting herbicides to thelocus; wherein said locus is: (a) a locus that contains: a plant or aseed capable of producing said plant; or (b) a locus that is to be aftersaid applying is made to contain the plant or the seed; wherein theplant or the seed comprises in at least some of its cells apolynucleotide operably linked to a promoter operable in plant cells,the promoter capable of expressing a wildtype or mutated CESApolypeptide encoded by the polynucleotide, the expression of thewildtype or mutated CESA polypeptide conferring to the plant toleranceto CESA-inhibiting herbicides.

Herbicide compositions hereof can be applied, e.g., as foliartreatments, soil treatments, seed treatments, or soil drenches.Application can be made, e.g., by spraying, dusting, broadcasting, orany other mode known useful in the art.

In one embodiment, herbicides can be used to control the growth of weedsthat may be found growing in the vicinity of the herbicide-tolerantplants invention. In embodiments of this type, an herbicide can beapplied to a plot in which herbicide-tolerant plants of the inventionare growing in vicinity to weeds. An herbicide to which theherbicide-tolerant plant of the invention is tolerant can then beapplied to the plot at a concentration sufficient to kill or inhibit thegrowth of the weed. Concentrations of herbicide sufficient to kill orinhibit the growth of weeds are known in the art and are disclosedabove.

In other embodiments, the present invention provides a method forcontrolling weeds in the vicinity of a CESA-inhibitingherbicides-tolerant plant of the invention. The method comprisesapplying an effective amount of a CESA-inhibiting herbicides to theweeds and to the herbicide-tolerant plant, wherein the plant hasincreased tolerance to CESA-inhibiting herbicide when compared to awild-type plant. In some embodiments, the CESA-inhibitingherbicides-tolerant plants of the invention are preferably crop plants,including, but not limited to, sunflower, alfalfa, Brassica sp.,soybean, cotton, safflower, peanut, tobacco, tomato, potato, wheat,rice, maize, sorghum, barley, rye, millet, and sorghum.

In other aspects, herbicide(s) (e.g., CESA-inhibiting herbicides) canalso be used as a seed treatment. In some embodiments, an effectiveconcentration or an effective amount of herbicide(s), or a compositioncomprising an effective concentration or an effective amount ofherbicide(s) can be applied directly to the seeds prior to or during thesowing of the seeds. Seed Treatment formulations may additionallycomprise binders and optionally colorants.

Binders can be added to improve the adhesion of the active materials onthe seeds after treatment. In one embodiments, suitable binders areblock copolymers EO/PO surfactants but also polyvinylalcoholsl,polyvinylpyrrolidones, polyacrylates, polymethacrylates, polybutenes,polyisobutylenes, polystyrene, polyethyleneamines, polyethyleneamides,polyethyleneimines (Lupasol(R), Polymin(R)), polyethers, polyurethans,polyvinylacetate, tylose and copolymers derived from these polymers.Optionally, also colorants can be included in the formulation. Suitablecolorants or dyes for seed treatment formulations are Rhodamin B, C.I.Pigment Red 112, C.I. Solvent Red 1, pigment blue 15:4, pigment blue15:3, pigment blue 15:2, pigment blue 15: 1, pigment blue 80, pigmentyellow 1, pigment yellow 13, pigment red 1 12, pigment red 48:2, pigmentred 48: 1, pigment red 57: 1, pigment red 53:1, pigment orange 43,pigment orange 34, pigment orange 5, pigment green 36, pigment green 7,pigment white 6, pigment brown 25, basic violet 10, basic violet 49,acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23,basic red 10, basic red 108.

The term seed treatment comprises all suitable seed treatment techniquesknown in the art, such as seed dressing, seed coating, seed dusting,seed soaking, and seed pelleting. In one embodiment, the presentinvention provides a method of treating soil by the application, inparticular into the seed drill: either of a granular formulationcontaining the CESA-inhibiting herbicides as a composition/formulation(e.g., a granular formulation), with optionally one or more solid orliquid, agriculturally acceptable carriers and/or optionally with one ormore agriculturally acceptable surfactants. This method isadvantageously employed, for example, in seedbeds of cereals, maize,cotton, and sunflower.

The present invention also comprises seeds coated with or containingwith a seed treatment formulation comprising CESA-inhibiting herbicidesand at least one other herbicide such as, e.g., an AHAS-inhibitorselected from the group consisting of amidosulfuron, azimsulfuron,bensulfuron, chlorimuron, chlorsulfuron, cinosulfuron, cyclosulfamuron,ethametsulfuron, ethoxysulfuron, flazasulfuron, flupyrsulfuron,foramsulfuron, halosulfuron, imazosulfuron, iodosulfuron, mesosulfuron,metsulfuron, nicosulfuron, oxasulfuron, primisulfuron, prosulfuron,pyrazosulfuron, rimsulfuron, sulfometuron, sulfosulfuron,thifensulfuron, triasulfuron, tribenuron, trifloxysulfuron,triflusulfuron, tritosulfuron, imazamethabenz, imazamox, imazapic,imazapyr, imazaquin, imazethapyr, cloransulam, diclosulam, florasulam,flumetsulam, metosulam, penoxsulam, bispyribac, pyriminobac,propoxycarbazone, flucarbazone, pyribenzoxim, pyriftalid andpyrithiobac.

The term “coated with and/or containing” generally signifies that theactive ingredient is for the most part on the surface of the propagationproduct at the time of application, although a greater or lesser part ofthe ingredient may penetrate into the propagation product, depending onthe method of application. When the said propagation product is(re)planted, it may absorb the active ingredient.

In some embodiments, the seed treatment application with CESA-inhibitingherbicides or with a formulation comprising the CESA-inhibitingherbicides is carried out by spraying or dusting the seeds before sowingof the plants and before emergence of the plants.

In other embodiments, in the treatment of seeds, the correspondingformulations are applied by treating the seeds with an effective amountof CESA-inhibiting herbicides or a formulation comprising theCESA-inhibiting herbicides.

In other aspects, the present invention provides a method for combatingundesired vegetation or controlling weeds comprising contacting theseeds of the CESA-inhibiting herbicides-tolerant plants of the presentinvention before sowing and/or after pregermination with CESA-inhibitingherbicides. The method can further comprise sowing the seeds, forexample, in soil in a field or in a potting medium in greenhouse. Themethod finds particular use in combating undesired vegetation orcontrolling weeds in the immediate vicinity of the seed. The control ofundesired vegetation is understood as the killing of weeds and/orotherwise retarding or inhibiting the normal growth of the weeds. Weeds,in the broadest sense, are understood as meaning all those plants whichgrow in locations where they are undesired.

The weeds of the present invention include, for example, dicotyledonousand monocotyledonous weeds. Dicotyledonous weeds include, but are notlimited to, weeds of the genera: Sinapis, Lepiclium, Galium, Stellaria,Matricaria, Anthemis, Galinsoga, Chenopodium, Urtica, Senecio,Amaranthus, Portulaca, Xanthium, Convolvulus, Ipomoea, Polygonum,Sesbania, Ambrosia, Cirsium, Carduus, Sonchus, Solarium, Rorippa,Rotala, Lindernia, Lamium, Veronica, Abutilon, Emex, Datura, Viola,Galeopsis, Papaver, Centaurea, Trifolium, Ranunculus, and Taraxacum.Monocotyledonous weeds include, but are not limited to, weeds of thegenera: Echinochloa, Setaria, Panicum, Digitaria, Phleum, Poa, Festuca,Eleusine, Brachiaria, Lolium, Bromus, Avena, Cyperus, Sorghum,Agropyron, Cynodon, Monochoria, Fimbristyslis, Sagittaria, Eleocharis,Scirpus, Paspalum, Ischaemum, Sphenoclea, Dactyloctenium, Agrostis,Alopecurus, and Apera.

In addition, the weeds of the present invention can include, forexample, crop plants that are growing in an undesired location. Forexample, a volunteer maize plant that is in a field that predominantlycomprises soybean plants can be considered a weed, if the maize plant isundesired in the field of soybean plants.

In other embodiments, in the treatment of seeds, the correspondingformulations are applied by treating the seeds with an effective amountof CESA-inhibiting herbicides or a formulation comprising theCESA-inhibiting herbicides.

In still further aspects, treatment of loci, plants, plant parts, orseeds of the present invention comprises application of an agronomicallyacceptable composition that does not contain an A.I. In one embodiment,the treatment comprises application of an agronomically acceptablecomposition that does not contain a CESA-inhibiting herbicides A.I. Insome embodiments, the treatment comprises application of anagronomically acceptable composition that does not contain aCESA-inhibiting herbicides A.L, wherein the composition comprises one ormore of agronomically-acceptable carriers, diluents, excipients, plantgrowth regulators, and the like. In other embodiments, the treatmentcomprises application of an agronomically acceptable composition thatdoes not contain a CESA-inhibiting herbicides A.I., wherein thecomposition comprises an adjuvant. In one embodiment, the adjuvant is asurfactant, a spreader, a sticker, a penetrant, a drift-control agent, acrop oil, an emulsifier, a compatibility agent, or combinations thereof.

It should also be understood that the foregoing relates to preferredembodiments of the present invention and that numerous changes may bemade therein without departing from the scope of the invention. Theinvention is further illustrated by the following examples, which arenot to be construed in any way as imposing limitations upon the scopethereof. On the contrary, it is to be clearly understood that resort maybe had to various other embodiments, modifications, and equivalentsthereof, which, after reading the description herein, may suggestthemselves to those skilled in the art without departing from the spiritof the present invention and/or the scope of the appended claims.

EXAMPLES Example 1: Identification of Cellulose Biosynthesis Inhibitor(CBI; CESA Inhibitor) Resistant Plants

For selection of cellulose biosynthesis inhibitor resistant plants EMSmutagenized seed populations of Arabidopsis thaliana are used. EMSmutagenized seed populations are either bought from Lehle Seeds (1102South Industrial Blvd. Suite D, Round Rock, Tex. USA) or are generatedas described elsewhere (Heim D R, et. al. (1989) Plant Physiol. 90:146-150). Causative mutations in CESA wildtype sequences (e.g. SEQ IDNO: 1 or 3) are identified as described by Scheible W R et. al. (2001,Proc. Natl. Acad. of Sci. 98: 10079-10084), McCourt et. al.(WO2013/142968) or with the use of next generation sequencing methods asdescribed by Austin R S, et. al. (2011) Plant Journal 67: 715-725.

Selected Arabidopsis thaliana lines were assayed for improved resistanceto azines like6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine;6-(1-fluoro-1-methyl-ethyl)-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine;6-cyclohexyl-N2-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine;6-(2,6-difluorophenyl)-N2-(2,3,5,6-tetrafluorophenyI)-1,3,5-triazine-2,4-diamine;N2-(4-chloro-3,5,6-trifluoro-2-pyridyl)-6-(1-fluoro-1-methyl-ethyl)-1,3,5-triazine-2,4-diaminein 48-well plates. Therefore, M2 or M3 seeds are surface sterilized bystirring for 5 min in ethanol+water (70+30 by volume), rinsing one timewith ethanol+water (70+30 by volume) and two times with sterile,deionized water. The seeds are resuspended in 0.1% agar dissolved inwater (w/v) Four to five seeds per well are plated on solid nutrientmedium consisting of half-strength murashige skoog nutrient solution, pH5.8 (Murashige and Skoog (1962) Physiologia Plantarum 15: 473-497).Compounds are dissolved in dimethylsulfoxid (DMSO) and added to themedium prior solidification (final DMSO concentration 0.1%). Multi wellplates are incubated in a growth chamber at 22° C., 75% relativehumidity and 110 μmol Phot*m⁻²*s⁻¹ with 14:10 h light:dark photoperiod.Growth inhibition is evaluated seven to ten days after seeding incomparison to wild type plants. Tolerance factors are calculated basedon IC50 values of growth inhibition of transformed versusnon-transformed Arabidopsis plants (Table 3).

TABLE 3 Tolerance of cellulose synthase mutant lines compared towildtype plants. Relative tolerance rates of mutant Arabidopsis linescompared to a wildtype Arabidopsis plants (wildtype = 1.0), treated withvarious cellulose biosynthesis inhibitors. Growth inhibition isevaluated seven to ten days after seeding in comparison to wild typeplants. N2-(4- 6- 6-(1-fluoro- 6- 6-(2,6- chloro-3,5,6- cyclopentyl-1-methyl- cyclohexyl- difluorophe- trifluoro-2- N4- ethyl)-N4- N2-nyl)-N2- pyridyl)-6-(1- (2,3,4,5,6- (2,3,4,5,6- (2,3,4,5,6- (2,3,5,6-fluoro-1- pentafluoro- pentafluoro- pentafluoro- tetrafluorophe- methyl-phenyl)-1,3,5- phenyl)-1,3,5- phenyl)-1,3,5- nyl)-1,3,5- ethyl)-1,3,5-triazine-2,4- triazine-2,4- triazine-2,4- triazine-2,4- triazine-2,4-Mutant diamine diamine diamine diamine diamine wildtype 1 1 1 1 1Cesa3_S1040L 56 2 10 13 4 Cesa3_S1037F 75 4 1 1 10 Cesa3_S983F 75 1 1 14 Cesa1_G1013R 25 4 4 13 10 Cesa1_P1010L 3 1 1 2 1 Cesa1_G1009D 3 2 1 11

Additionally, M2 or M3 Arabidopsis plants are tested for improvedtolerance to cellulose biosynthesis-inhibiting herbicides in greenhousestudies (e. g. with the following cellulose biosynthesis-inhibitingherbicides:6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine;6-(1-fluoro-1-methyl-ethyl)-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine;N4-(4-chloro-3,5,6-trifluoro-2-pyridyl)-6-(1-fluoro-1-methyl-ethyl)-1,3,5-triazine-2,4-diamine;6-(2,6-difluorophenyl)-N4-(2,3,5,6-tetrafluorophenyl)-1,3,5-triazine-2,4-diamine;N4-(4-bromo-2,3,5,6-tetrafluoro-phenyl)-6-(1-fluoro-1-methyl-ethyl)-1,3,5-triazine-2,4-diamine.

TABLE 4 Phytotox values of cellulose synthase mutant lines to variouscellulose biosynthesis inhibitors when treated pre-emergent. Shown arephytotox values on a scale from 0-100, were 100 is 100% damage.Cesa3_(—) Cesa3_(—) Cesa3_(—) Cesa1_(—) Cesa1_(—) Cesa1_(—) A. thalianaS1040L, S1037F, S983F, G1013R, P1010L, G1009D, compound g ai/ha WT L.erecta fpx1-1 fpx1-2 fpx1-3 fpx2-1 fpx2-2 fpx2-36-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)- 15.63 100 40 5 40 15 9888 1,3,5-triazine-2,4-diamine 3.91 99 25 15 20 25 63 58 0.98 80 20 23 515 33 25 0.25 38 5 0 0 5 0 51-(m-tolyl)-5-phenyl-1,2,4-triazole-3-carboxamide 250 100 25 68 30 15 3545 62.5 100 0 23 5 20 13 30 15.63 63 30 30 8 15 20 18 3.91 0 38 0 0 5 00 6-(1-fluoro-1-methyl-ethyl)-N4-(2,3,4,5,6- 3.91 100 98 80 98 97 100100 pentafluorophenyl)-1,3,5-triazine-2,4-diamine 0.98 100 75 30 75 6399 97 0.25 78 65 20 45 65 50 78 0.0625 38 20 10 78 13 43 65N4-(4-chloro-3,5,6-trifluoro-2-pyridyl)-6-(1-fluoro- 3.91 99 53 25 13 8098 99 1-methyl-ethyl)-1,3,5-triazine-2,4-diamine 0.98 83 78 25 48 70 7893 0.25 60 15 15 55 50 25 43 0.0625 45 13 5 23 40 50 306-(2,6-difluorophenyl)-N4-(2,3,5,6- 62.5 100 28 99 33 40 98 95tetrafluorophenyl)-1,3,5-triazine-2,4-diamine 15.63 90 25 73 43 28 65 183.91 70 8 65 35 35 35 38 0.98 30 13 28 18 15 48 65N4-(4-bromo-2,3,5,6-tetrafluoro-phenyl)-6-(1- 15.63 100 93 30 45 73 9999 fluoro-1-methyl-ethyl)-1,3,5-triazine-2,4-diamine 3.91 97 63 33 25 3588 68 0.98 35 5 18 23 10 25 35 0.25 8 13 28 35 10 25 50

TABLE 5 Phytotox values of cellulose synthase mutant lines to variouscellulose biosynthesis inhibitors when treated post-emergent, 6 weeksafter sowing. Shown are phytotox values on a scale from 0-100, were 100is 100% damage. Cesa3_(—) Cesa3_(—) Cesa3_(—) Cesa1_(—) Cesa1_(—)Cesa1_(—) A. thaliana S1040L, S1037F, S983F, G1013R, P1010L, G1009D,compound g ai/ha WT L. erecta fpx1-1 fpx1-2 fpx1-3 fpx2-1 fpx2-2 fpx2-36-cyclopentyl-N4-(2,3,4,5,6- 63 98 68 78 73 80 93 75pentafluorophenyl)-1,3,5-triazine-2,4- 31.5 78 35 70 55 65 78 73 diamine15.75 80 5 58 65 55 70 63 7.88 68 0 55 25 38 63 451-(m-tolyl)-5-phenyl-1,2,4-triazole-3- 250 95 55 68 53 40 48 45carboxamide 125 83 23 50 23 33 15 33 62.5 78 0 30 28 23 15 23

Example 2: Identification of Homologue Cellulose Synthase Isoforms inCrop Plants

To identify homologue cellulose synthase genes from soy, corn and rice,BLAST searches using the protein sequences of Arabidopsis thalianacellulose synthase isoforms were performed (Altschul et al. (1990) J MolBiol 215: 403-10). Cellulose synthase protein encoding genes from corn,soy and rice were analyzed regarding their phylogenetic relationship bythe R software library phangorn (Schliep K P. (2011) Bioinformatics 27:592-593). Bootstrap analyses to statistically confirm monophyleticgroups were calculated. In addition genes were classified by theirexpression level and expression pattern (Hruz T, et. al. (2008) Adv. inBioinformatics 2008: 1-5) (FIG. 1-3) and selected for planttransformation.

Example 3: Tissue Culture Conditions

An in vitro tissue culture mutagenesis assay is developed to isolate andcharacterize plant tissue (e.g., maize, rice) that is tolerant tocellulose synthase inhibiting herbicides, (e. g.6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine,and photosynthesis inhibitor diuron as negative control). The assayutilizes the somaclonal variation that is found in in vitro tissueculture. Spontaneous mutations derived from somaclonal variation can beenhanced by chemical mutagenesis (e. g. ethylmethane sulfonate;ethylethane sulfonate, N-nitroso-N-ethyl urea, ethylnitrosourea, nitroseacid, bromouracil, 2.-aminopurine, 5-fluorodeoxyuridine, hydroxylamine,N-methyl-N′-nitro-N-nitrosoguanidine) and subsequent selection in astepwise manner, on increasing concentrations of herbicide.

The present invention provides tissue culture conditions for encouraginggrowth of friable, embryogenic maize or rice callus that is regenerable.Calli are initiated from 4 different maize or rice cultivarsencompassing Zea mays and Japonica (Taipei 309, Nipponbare, Koshihikari)and Indica (Indica 1) varieties, respectively. Seeds are surfacesterilized in 70% ethanol for approximately 1 min followed by 20%commercial Clorox bleach for 20 minutes. Seeds are rinsed with sterilewater and plated on callus induction media. Various callus inductionmedia are tested. The ingredient lists for the media tested arepresented in Table 6.

TABLE 6 Ingredient Supplier R001M R025M R026M R327M R008M MS711R B5Vitamins Sigma 1.0 X MS salts Sigma 1.0 X 1.0 X 1.0 X 1.0 X MS VitaminsSigma 1.0 X 1.0 X N6 salts Phytotech 4.0 g/L 4.0 g/L N6 vitaminsPhytotech 1.0 X 1.0 X L-Proline Sigma 2.9 g/L 0.5 g/L 1.2 g/L CasaminoAcids BD 0.3 g/L 0.3 g/L 2 g/L Casein Sigma 1.0 g/L Hydrolysate L-AspPhytotech 150 mg/L Monohydrate Nicotinic Acid Sigma 0.5 mg/L PyridoxineHCl Sigma 0.5 mg/L Thiamine HCl Sigma 1.0 mg/L Myo-inositol Sigma 100mg/L MES Sigma 500 mg/L 500 mg/L 500 mg/L 500 mg/L 500 mg/L 500 mg/LMaltose VWR 30 g/L 30 g/L 30 g/L 30 g/L Sorbitol Duchefa 30 g/L SucroseVWR 10 g/L 30 g/L NAA Duchefa 50 μg/L 2,4-D Sigma 2.0 mg/L 1.0 mg/LMgCl₂•6H₂O VWR 750 mg/L →pH 5.8 5.8 5.8 5.8 5.8 5.7 Gelrite Duchefa 4.0g/L 2.5 g/L Agarose Type1 Sigma 7.0 g/L 10 g/L 10 g/L →Autoclave 15 min15 min 15 min 15 min 15 min 20 min Kinetin Sigma 2.0 mg/L 2.0 mg/L NAADuchefa 1.0 mg/L 1.0 mg/L ABA Sigma 5.0 mg/L Cefotaxime Duchefa 0.1 g/L0.1 g/L 0.1 g/L Vancomycin Duchefa 0.1 g/L 0.1 g/L 0.1 g/L G418Disulfate Sigma 20 mg/L 20 mg/L 20 mg/L

R001M callus induction media was selected after testing numerousvariations. Cultures were kept in the dark at 30° C. Embryogenic calluswas subcultured to fresh media after 10-14 days.

Example 4: Selection of Herbicide-Tolerant Calli

Once tissue culture conditions were determined, further establishment ofselection conditions are established through the analysis of tissuesurvival in kill curves with azine herbicides e. g. like6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine,and photosynthesis inhibitor diuron as negative control. Carefulconsideration of accumulation of the herbicide in the tissue, as well asits persistence and stability in the cells and the culture media areperformed. Through these experiments, a sub-lethal dose is establishedfor the initial selection of mutated material. After the establishmentof the starting dose of azine herbicides like e. g.6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine,and photosynthesis inhibitor diuron as negative control in selectionmedia, the tissues were selected in a step-wise fashion by increasingthe concentration of the cellulose synthase inhibitor with each transferuntil cells are recovered that grew vigorously in the presence of toxicdoses. The resulting calli are further subcultured every 3-4 weeks toR001M with selective agent. Over 26,000 calli are subjected to selectionfor 4-5 subcultures until the selective pressure is above toxic levelsas determined by kill curves and observations of continued culture.Alternatively, liquid cultures initiated from calli in MS711R with slowshaking and weekly subcultures. Once liquid cultures are established,selection agent is added directly to the flask at each subculture.Following 2-4 rounds of liquid selection, cultures are transferred tofilters on solid R001M media for further growth.

Example 5: Regeneration of Plants

Tolerant tissue is regenerated and characterized molecularly forcellulose synthase gene sequences mutations. In addition, genes involveddirectly and/or indirectly in cell wall biosynthesis and/or metabolismpathways are also sequenced to characterize mutations. Finally, enzymesthat change the fate (e.g. metabolism, translocation, transportation)are also sequenced to characterize mutations. Following herbicideselection, calli are regenerated using a media regime of R025M for 10-14days, R026M for ca. 2 weeks, R327M until well formed shoots weredeveloped, and R008S until shoots are well rooted for transfer to thegreenhouse. Regeneration was carried out in the light. No selectionagent is included during regeneration. Once strong roots areestablished, MO regenerants are transplant to the greenhouse in squareor round pots. Transplants are maintained under a clear plastic cupuntil they were adapted to greenhouse conditions. The greenhouse was setto a day/night cycle of 27° C./21° C. (80° F./70° F.) with 600 W highpressure sodium lights supplementing light to maintain a 14 hour daylength. Plants are watered according to need, depending in the weatherand fertilized daily.

Example 6: Sequence Analysis

Leaf tissue is collected from clonal plants separated for transplantingand analyzed as individuals. Genomic DNA is extracted using a Wizard® 96Magnetic DNA Plant System kit (Promega, U.S. Pat. Nos. 6,027,945 &6,368,800) as directed by the manufacturer. Isolated DNA is PCRamplified using the appropriate forward and reverse primer.

PCR amplification is performed using Hotstar Taq DNA Polymerase (Qiagen)using touchdown thermocycling program as follows: 96° C. for 15 min,followed by 35 cycles (96° C., 30 sec; 58° C.-0.2° C. per cycle, 30 sec;72° C., 3 min and 30 sec), 10 min at 72° C. PCR products were verifiedfor concentration and fragment size via agarose gel electrophoresis.Dephosphorylated PCR products are analyzed by direct sequence using thePCR primers (DNA Landmarks). Chromatogram trace files (.scf) areanalyzed for mutation relative to the wild-type gene using Vector NTIAdvance 10™ (Invitrogen). Based on sequence information, mutations areidentified in several individuals. Sequence analysis is performed on therepresentative chromatograms and corresponding AlignX alignment withdefault settings and edited to call secondary peaks.

Example 7: Engineering Azine-Tolerant Arabidopsis Plants Having Wildtypeor Mutated Cellulose Synthase Sequences

For transformation of Arabidopsis thaliana, wildtype or mutatedcellulose synthase sequences based on one of the following sequences SEQID NO: 72, 73, 74, 75, 76, or 77, are cloned with standard cloningtechniques as described in Sambrook et al. (Molecular cloning (2001)Cold Spring Harbor Laboratory Press) in a binary vector containingresistance marker gene cassette (AHAS) and mutated cellulose synthasesequence (marked as GOD in between ubiquitin promoter (PcUbi) andnopaline synthase terminator (NOS) sequence. Binary plasmids areintroduced to Agrobacterium tumefaciens for plant transformation.Arabidopsis thaliana are transformed with wildtype or mutated cellulosesynthase sequences by floral dip method as decribed by McElver and Singh(WO 2008/124495). Transgenic Arabidopsis plants are subjected to TaqMananalysis for analysis of the number of integration loci.

Transgenic Arabidopsis thaliana plants are assayed for improvedtolerance to azine herbicides like e. g.6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diaminein 48-well plates. Therefore, T2 seeds are surface sterilized bystirring for 5 min in ethanol+water (70+30 by volume), rinsing one timewith ethanol+water (70+30 by volume) and two times with sterile,deionized water. The seeds are resuspended in 0.1% agar dissolved inwater (w/v) Four to five seeds per well are plated on solid nutrientmedium consisting of half-strength murashige skoog nutrient solution, pH5.8 (Murashige and Skoog (1962) Physiologia Plantarum 15: 473-497).Compounds are dissolved in dimethylsulfoxid (DMSO) and added to themedium prior solidification (final DMSO concentration 0.1%). Multi wellplates are incubated in a growth chamber at 22° C., 75% relativehumidity and 110 μmol Phot*m⁻²*s⁻¹ with 14:10 h light:dark photoperiod.Growth inhibition is evaluated seven to ten days after seeding incomparison to wild type plants. Tolerance factors are calculated basedon IC50 values of growth inhibition of transformed versusnon-transformed Arabidopsis plants.

TABLE 7 Relative tolerance rates of transgenic Arabidopsis plants ascompared to a non-transgenic Arabidopsis plant (non-transgenic = 1.0),treated with various cellulose biosynthesis inhibitors. Growthinhibition is evaluated seven to ten days after seeding in comparison towild type plants. construct AtCESA1 wt AtCESA1_G1013R AtCESA3_wtAtCESA3_S1040L AtCESA3_S1037F SEQ ID NO 1 1 3 3 3 substitution — G1013R— S1040L S1037F 1-(m-tolyl)-5-phenyl-1,2,4-triazole-3-carboxamide 3 33 4 2 1333 6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)- 1 3 1 1 171,3,5-triazine-2,4-diamine

Additionally, transgenic T2 Arabidopsis plants are tested for improvedtolerance to CESA-inhibiting herbicides in greenhouse studies with azinecompounds like e.g.6-cyclopentyl-N4-(2,3,4,5,6-pentafluorophenyl)-1,3,5-triazine-2,4-diamine.

Example 8: Soybean Transformation and Cellulose Biosynthesis InhibitorTolerance Testing

Binary vectors are generated as described in EXAMPLE 7. Soybean cv Jakeare transformed as previously described by Siminszky et al., PhytochemRev. 5:445-458 (2006). After regeneration, transformants aretransplanted to soil in small pots, placed in growth chambers (16 hrday/8 hr night; 25° C. day/23° C. night; 65% relative humidity; 130-150microE m−2 s−1) and subsequently tested for the presence of the T-DNAvia Taqman analysis. After a few weeks, healthy, transgenic positive,single copy events are transplanted to larger pots and allowed to growin the growth chamber. An optimal shoot for cutting is about 3-4 inchestall, with at least two nodes present. Each cutting is taken from theoriginal transformant (mother plant) and dipped into rooting hormonepowder (indole-3-butyric acid, IBA). The cutting is then placed in oasiswedges inside a bio-dome. The mother plant is taken to maturity in thegreenhouse and harvested for seed. Wild type cuttings are also takensimultaneously to serve as negative controls. The cuttings are kept inthe bio-dome for 5-7 days. 3-4 days after transfer to oasis wedges, theshoots are treated via nutrient solution with the herbicide. Typicalphytotox symptoms, like club shaped root, are evaluated 3-4 days aftertreatment. Less or no injury of transgenic plants compared to wildtypeplants are interpreted as herbicide tolerance.

Example 9: Engineering Cellulose Biosynthesis Inhibitor Tolerant Corn orRice Plants Having Mutated Cellulose Synthase Sequences

Immature embryos can be transformed according to the procedure outlinedin Peng et al. (WO2006/136596). Plants are tested for the presence ofthe T-DNA by Taqman analysis with the target being the nos terminatorwhich is present in all constructs. Healthy looking plants are sent tothe greenhouse for hardening and subsequent spray testing. The plantsare individually transplanted into MetroMix 360 soil in 4″ pots. Once inthe greenhouse (day/night cycle of 27° C./21° C. with 14 hour day lengthsupported by 600 W high pressure sodium lights), they are allowed togrow for 14 days. Transformation of Oryza sativa (rice) are done byprotoplast transformation as described by Peng et al. (U.S. Pat. No.6,653,529). Transgenic corn and rice plants are cultivated to T1 seedsfor herbicide tolerance testing.

Example 10: Demonstration of Herbicide Tolerance

T0 or T1 transgenic plant of soybean, corn and rice containing cellulosesynthase sequences or mutated gene variants thereof are tested forimproved tolerance to herbicides in greenhouse studies and mini-plotstudies with azine herbicides. For the pre-emergence treatment, theherbicides are applied directly after sowing by means of finelydistributing nozzles. The containers are irrigated gently to promotegermination and growth and subsequently covered with transparent plastichoods until the plants have rooted. This cover causes uniformgermination of the test plants, unless this has been impaired by theherbicides. For post emergence treatment, the test plants are firstgrown to a height of 3 to 15 cm, depending on the plant habit, and onlythen treated with the herbicides. For this purpose, the test plants areeither sown directly, and grown in the same containers or they are firstgrown separately and transplanted into the test containers a few daysprior to treatment.

Herbicide injury evaluations are taken at 2 and 3 weeks after treatment.Plant injury is rated on a scale of 0% to 100%, 0% being no injury and100% being complete death.

The following gives a definition of the injury scores measured above:

Score Description of injury 0 No Injury 1 Minimal injury, only a fewpatches of leaf injury or chlorosis. 2 Minimal injury with slightlystronger chlorosis. Overall growth points remain undamaged. 3 Slightlystronger injury on secondary leaf tissue, but primary leaf and growthpoints are still undamaged. 4 Overall plant morphology is slightlydifferent, some chlorosis and necrosis in secondary growth points andleaf tissue. Stems are intact. Regrowth is highly probable within 1week. 5 Overall plant morphology is clearly different, some chlorosisand necrosis on a few leaves and growth points, but primary growth pointis intact. Stem tissue is still green. Regrowth is highly probablywithin 1 week. 6 Strong injury can be seen on the new leaflet growth.Plant has a high probability to survive only through regrowth atdifferent growth points. Most of the leaves are chlorotic/necrotic butstem tissue is still green. May have regrowth but with noticeableinjured appearance. 7 Most of the active growth points are necrotic.There may be a single growth point that could survive and may bepartially chlorotic or green and partially necrotic. Two leaves maystill be chlorotic with some green; the rest of the plant including stemis necrotic. 8 Plant will likely die, and all growth points arenecrotic. One leaf may still be chlorotic with some green. The remainderof the plant is necrotic. 9 Plant is dead. * Not tested

The invention claimed is:
 1. A method for controlling weeds at a locusfor growth of a plant, the method comprising: (a) applying an herbicidecomposition comprising a CESA-inhibiting herbicide to the locus; and (b)planting a seed at the locus, wherein the seed is capable of producing aplant that comprises in at least some of its cells a polynucleotideoperably linked to a promoter operable in plant cells, the promotercapable of expressing a wildtype or mutated CESA polypeptide encoded bythe polynucleotide, the expression of the wildtype or mutated CESApolypeptide conferring to the plant tolerance to CESA-inhibitingherbicides, wherein the mutated CESA polypeptide comprises one or moreof the following motifs: i) Motif 1a: (SEQ ID NO: 78) [V/I][A/V]G [V/I/F] [S/T] [Y/D/N/A]A [V/I/L] [N/S/G] [S/N]G [Y/F/E][Q/D/G/E/H] [S/A]WG [P/A]L [F/M/L]G [K/R] [L/V] [F/L]F,

wherein the amino acid at position 5, 16, 17, and/or 20 within saidmotif is substituted by any other amino acid; ii) Motif 2a:(SEQ ID NO: 81) [V/L/I]W [S/A] [V/A/I]LL [A/S]S [I/F/V] [F/L][S/T] [L/V][L/M/V/I] WV [R/K] [I/V] [N/D]PF

wherein the amino acid at position 8 and/or 11 within said motif issubstituted by any other amino acid, wherein the CESA-inhibitingherbicide comprises a compound having the Formula (I):

wherein A is heteroaryl, which is substituted by 1, 2, 3, 4, 5 or 6substituents R^(A) selected from the group consisting of halogen, OH,CN, amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkoxy,C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy, (C₁-C₆-alkoxy)-C₁-C₆-alkyl,(C₁-C₆-alkoxy)-C₁-C₆-alkoxy, (C₁-C₆-alkoxy)-C₂-C₆-alkenyl,(C₁-C₆-alkoxy)-C₂-C₆-alkynyl, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,(C₁-C₆-alkyl)sulfonyl, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,(C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,(C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,(C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, and (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,where the aliphatic and cycloaliphatic parts of the 22 aforementionedradicals are unsubstituted, partly or completely halogenated and wherethe cycloaliphatic parts of the last 4 mentioned radicals may carry 1,2, 3, 4, 5 or 6 methyl groups; R¹ is selected from the group consistingof H, OH, S(O)₂NH₂, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,(C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,(C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,(C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,(C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,(C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and(C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts ofthe 14 aforementioned radicals are unsubstituted, partly or completelyhalogenated, or phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl,phenylaminosulfonyl, phenylcarbonyl and phenoxycarbonyl, wherein phenylin the last 6 mentioned radicals are unsubstituted or substituted by 1,2, 3, 4 or 5 identical or different substituents selected from the groupconsisting of halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₁-C₆-alkoxy and C₁-C₆-haloalkoxy; R² is H, halogen, OH, CN,C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl, (C₁-C₆-alkoxy)-C₁-C₆-alkyl,C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl,C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy or(C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and cycloaliphaticparts of the 9 aforementioned radicals are unsubstituted, partly orcompletely halogenated, or phenyl or phenyl-C₁-C₆-alkyl, wherein phenylin the last 2 mentioned radicals are unsubstituted or substituted by 1,2, 3, 4 or 5 identical or different substituents selected from the groupconsisting of halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₁-C₆-alkoxy and C₁-C₆-haloalkoxy; R³ is selected from the groupconsisting of H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxyand C₁-C₆-haloalkoxy; R⁴ is selected from the group consisting of H,halogen, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl,C₃-C₆-cycloalkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkenyl andC₁-C₆-alkoxy-C₁-C₆-alkyl, where the aliphatic and cycloaliphatic partsof the 7 aforementioned radicals are unsubstituted, partly or completelyhalogenated; or R³ and R⁴ together with the carbon atom to which theyare attached form a moiety selected from the group consisting ofcarbonyl, C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl and three-to six-membered heterocyclyl, wherein the C₃-C₆-cycloalkyl,C₃-C₆-cycloalkenyl, or three- to six-membered heterocyclyl isunsubstituted or substituted by one to three substituents selected fromhalogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy; and R⁵ is selected from thegroup consisting of H, OH, S(O)₂NH₂, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,(C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,(C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,(C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,(C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and(C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts ofthe 14 aforementioned radicals are unsubstituted, partly or completelyhalogenated, or phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl,phenylaminosulfonyl, phenylcarbonyl and phenoxycarbonyl, wherein phenylin the last 6 mentioned radicals are unsubstituted or substituted by 1,2, 3, 4 or 5 identical or different substituents selected from the groupconsisting of halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₁-C₆-alkoxy and C₁-C₆-haloalkoxy.
 2. The method of claim 1, whereinherbicide composition is applied to the weeds and to the plant producedby the seed.
 3. A method for controlling weeds at a locus for growth ofa plant, the method comprising: (a) applying an herbicide compositioncomprising a CESA-inhibiting herbicide to the locus; and (b) planting aseed at the locus, wherein the seed is capable of producing a plant thatcomprises in at least some of its cells a polynucleotide operably linkedto a promoter operable in plant cells, the promoter capable ofexpressing a wildtype or mutated CESA polypeptide encoded by thepolynucleotide, the expression of the wildtype or mutated CESApolypeptide conferring to the plant tolerance to CESA-inhibitingherbicides, wherein the mutated CESA polypeptide comprises one or moreof the following motifs: i) Motif 1a: (SEQ ID NO: 78) [V/I][A/V]G [V/I/F] [S/T] [Y/D/N/A]A [V/I/L] [N/S/G] [S/N]G [Y/F/E][Q/D/G/E/H] [S/A]WG [P/A]L [F/M/L]G [K/R] [L/V] [F/L]F,

wherein the amino acid at position 5, 16, and/or 17, within said motifis substituted by any other amino acid; ii) Motif 2a: (SEQ ID NO: 81)[V/L/I]W [S/A] [V/A/I]LL [A/S]S [I/F/V] [F/L][S/T] [L/V] [L/M/V/I]WV [R/K] [I/V] [N/D]PF

wherein the amino acid at position 8 and/or 11 within said motif issubstituted by any other amino acid.
 4. The method of claim 3, whereinherbicide composition is applied to the weeds and to the plant producedby the seed.
 5. The method of claim 3, wherein the CESA-inhibitingherbicide comprises a compound having the Formula (I):

wherein A is heteroaryl, which is substituted by 1, 2, 3, 4, 5 or 6substituents R^(A) selected from the group consisting of halogen, OH,CN, amino, NO₂, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkoxy,C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy, (C₁-C₆-alkoxy)-C₁-C₆-alkyl,(C₁-C₆-alkoxy)-C₁-C₆-alkoxy, (C₁-C₆-alkoxy)-C₂-C₆-alkenyl,(C₁-C₆-alkoxy)-C₂-C₆-alkynyl, C₁-C₆-alkylthio, (C₁-C₆-alkyl)sulfinyl,(C₁-C₆-alkyl)sulfonyl, (C₁-C₆-alkyl)amino, di(C₁-C₆-alkyl)amino,(C₁-C₆-alkyl)-carbonyl, (C₁-C₆-alkoxy)-carbonyl,(C₁-C₆-alkyl)-carbonyloxy, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkoxy,(C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, and (C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy,where the aliphatic and cycloaliphatic parts of the 22 aforementionedradicals are unsubstituted, partly or completely halogenated and wherethe cycloaliphatic parts of the last 4 mentioned radicals may carry 1,2, 3, 4, 5 or 6 methyl groups; R¹ is selected from the group consistingof H, OH, S(O)₂NH₂, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,(C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,(C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,(C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,(C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,(C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and(C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts ofthe 14 aforementioned radicals are unsubstituted, partly or completelyhalogenated, or phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl,phenylaminosulfonyl, phenylcarbonyl and phenoxycarbonyl, wherein phenylin the last 6 mentioned radicals are unsubstituted or substituted by 1,2, 3, 4 or 5 identical or different substituents selected from the groupconsisting of halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₁-C₆-alkoxy and C₁-C₆-haloalkoxy; R² is H, halogen, OH, CN,C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl, (C₁-C₆-alkoxy)-C₁-C₆-alkyl,C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl,C₁-C₆-alkoxy, C₂-C₆-alkenyloxy, C₂-C₆-alkynyloxy, C₃-C₆-cycloalkoxy or(C₃-C₆-cycloalkyl)-C₁-C₄-alkoxy, where the aliphatic and cycloaliphaticparts of the 9 aforementioned radicals are unsubstituted, partly orcompletely halogenated, or phenyl or phenyl-C₁-C₆-alkyl, wherein phenylin the last 2 mentioned radicals are unsubstituted or substituted by 1,2, 3, 4 or 5 identical or different substituents selected from the groupconsisting of halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₁-C₆-alkoxy and C₁-C₆-haloalkoxy; R³ is selected from the groupconsisting of H, halogen, CN, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxyand C₁-C₆-haloalkoxy; R⁴ is selected from the group consisting of H,halogen, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₃-C₆-alkynyl,C₃-C₆-cycloalkyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₃-C₆-cycloalkenyl andC₁-C₆-alkoxy-C₁-C₆-alkyl, where the aliphatic and cycloaliphatic partsof the 7 aforementioned radicals are unsubstituted, partly or completelyhalogenated; or R³ and R⁴ together with the carbon atom to which theyare attached form a moiety selected from the group consisting ofcarbonyl, C₂-C₆-alkenyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl and three-to six-membered heterocyclyl, wherein the C₃-C₆-cycloalkyl,C₃-C₆-cycloalkenyl, or three- to six-membered heterocyclyl isunsubstituted or substituted by one to three substituents selected fromhalogen, CN, C₁-C₆-alkyl and C₁-C₆-alkoxy; and R⁵ is selected from thegroup consisting of H, OH, S(O)₂NH₂, CN, C₁-C₆-alkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, (C₃-C₆-cycloalkyl)-C₁-C₄-alkyl, C₁-C₆-alkoxy,(C₁-C₆-alkoxy)-C₁-C₆-alkyl, (C₁-C₆-alkyl)-carbonyl,(C₁-C₆-alkoxy)carbonyl, (C₁-C₆-alkyl)sulfonyl,(C₁-C₆-alkylamino)carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,(C₁-C₆-alkylamino)sulfonyl, di(C₁-C₆-alkyl)aminosulfonyl and(C₁-C₆-alkoxy)sulfonyl, where the aliphatic and cycloaliphatic parts ofthe 14 aforementioned radicals are unsubstituted, partly or completelyhalogenated, or phenyl, phenyl-C₁-C₆-alkyl, phenylsulfonyl,phenylaminosulfonyl, phenylcarbonyl and phenoxycarbonyl, wherein phenylin the last 6 mentioned radicals are unsubstituted or substituted by 1,2, 3, 4 or 5 identical or different substituents selected from the groupconsisting of halogen, CN, NO₂, C₁-C₆-alkyl, C₁-C₆-haloalkyl,C₁-C₆-alkoxy and C₁-C₆-haloalkoxy.